Dopmin Synonyms. Dopamine, Dopamine Group of drugs. Medicines used for circulatory failure. Composition and release form. Solution for infusion in ampoules of 5 ml (1 ml of solution contains 40 mg of dopamine hydrochloride) in

Dopamine

Dopamine When a person receives some positive experience (and satisfaction of needs is certainly a positive experience) - eats or procreates (has sex), successfully studies or works, swims in the sea or dances - is produced in large quantities in his brain

So what does Dopamine have to do with it? Why do people take drugs if they pose such a deadly danger - they can get you in trouble with the police, ruin your career, and even die prematurely? It's all about dopamine. In the depths of your brain, in

Chapter 7 Why Wall Street Crash But Warren Buffett Is Still Thriving Introverts and Extroverts Think (and Respond to Dopamine) Differently

Chapter 7 Why Wall Street Crash But Warren Buffett Is Still Thriving Introverts and Extroverts Think Differently (and Respond to Dopamine) Tocqueville understood that in a world of constant action and decision-making that was shaped by

Systematic (IUPAC) name: 4-(2-aminoethyl)benzene-1,2-diol

Commercial names“Intropin”, “Revimin”, etc.

Legality℞ (dispensed strictly according to prescription)

Route of administration intravenous injections

Metabolism ADH, DBG, MAO-A, MAO-B, KOMT

Excretion Renal (with urine)

Synonyms 2-(3,4-dihydroxyphenyl)ethylamine; 3,4-dihydroxyphenethylamine; 3-hydroxytyramine; YES; intropin; revival; oxytyramine; prolactin inhibitory factor; hormone that inhibits the release of prolactin at the level of the adenohypophysis

Chem. formula C8H11NO2

Molecular weight 153.18 g/mol

Dopamine (abbreviated from 3,4-dihydroxyphenylamine) is a neurotransmitter of the catecholamine and phenethylamine families, which is necessary for the proper functioning of the brain and the body as a whole. Dopamine gets its name from its chemical composition: it is an amine formed by removing the carboxyl group from the L-DOPA molecule. In the brain, dopamine functions as a neurotransmitter (a substance secreted by nerve cells to transmit signals through it to other nerve cells). The brain contains several separate dopamine complexes, one of which is responsible for our motivation. Typically, when a person is “rewarded” for a job well done, dopamine levels in the brain increase (many drugs act on this principle by increasing the activity of dopamine neurons). Other dopamine complexes are responsible for the regulation of movement (motility) and regulate the production of several other important hormones. Some serious diseases of the nervous system develop due to dysfunction of dopamine complexes. Scientists have found that the degenerative disorder, which is accompanied by tremors and poor coordination of movements, is caused by the loss of neurons responsible for the production of dopamine in the midbrain (the so-called substantia nigra). According to some data, this background radically changes the degree of dopamine activity in the brain, and (drugs that are often used to treat this disease) mainly reduce dopamine activity. According to scientists, attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS) also develop against the background of decreased dopamine activity. In addition to the nervous system, dopamine also performs a number of functions in several other systems of the body, being, in fact, a chemical carrier of genetic information. In blood vessels, it inhibits the production of norepinephrine and acts as a vasodilator; in the kidneys, it stimulates renal excretion of sodium (together with urine); in the pancreas, dopamine slows down insulin synthesis; in the digestive system, it reduces gastrointestinal motility and protects the intestinal mucosa; In the immune system, dopamine reduces the activity of lymphocytes. After excretion from the blood vessels, in each of the above peripheral systems, dopamine performs a “paracrine” function: it is synthesized in specific areas, affecting cells located next to the cells responsible for its production. Some medications “change” the way dopamine affects the body. Dopamine enters the body in the form of intravenous injections: although it does not pass from the bloodstream directly to the brain, it affects the peripheral systems of the body (which is why it is often used for heart failure or shock (especially in newborns).), a metabolic precursor dopamine, penetrates the brain and is the most popular treatment for Parkinson's disease. Dopaminergic stimulants can be addictive and addictive (in high doses), while some of them have been successfully used to treat ADHD (we are talking about lower doses). on the contrary, the principle of action of many antipsychotics is based on partial inhibition of dopamine (that is, weakening of its action). These drugs (dopamine antagonists) fight nausea more effectively than others. Drugs containing dopamine hydrochloride are used in the treatment of acute heart failure, renal failure, myocardial infarction, septic shock, etc., and are included in the list of essential drugs of the World Health Organization (WHO-LPPN).

Physiological action

Dopaminergic systems

Brain

The main dopamine channels are concentrated here. While in the “reward” channel, dopamine is synthesized in the bodies of all nerve cells located within the ventral tegmental area (VTA), from where it enters the nucleus accumbens and prefrontal cortex. A separate channel is responsible for the motor functions of dopamine, in which the cell bodies of the substantia nigra are present (having been synthesized inside these cells, dopamine subsequently penetrates into the striatum. In the brain, dopamine plays an important role in controlling motor skills, it is also responsible for motivation, regulates the degree of activity of the central nervous system, forms cognitive function and the reward system, and is also responsible for lower-order functions, such as the production of breast milk in women, sexual satisfaction and nausea. There are not many dopaminergic neurons (that is, neurons whose main neurotransmitter is dopamine) (about 400,000 in total). in the human brain), and their cell bodies are concentrated in relatively small areas of the brain, from where their action is projected to many other areas of the brain, from where they reach “their goals.” Similar complexes of dopaminergic cells were first discovered in 1964 by Annika Dahlström and Kjell Fuchs. , who came up with their own designation for each of them (in alphabetical order: “A” - “aminergic”, etc.). In their system, areas A1 to A7 contain the neurotransmitter norepinephrine, while areas A8 to A14 contain dopamine. Below is a list of dopaminergic brain regions identified by these scientists:

Beyond the Nervous System

Dopamine does not cross the blood-brain barrier, so it is synthesized and functions in peripheral areas independent of synthesis and activity in the brain. A fairly decent amount of dopamine circulates in the blood, but its functions are not fully understood. Dopamine is also present in plasma (in the same concentrations as epinephrine), but in humans over 95% of plasma dopamine is in the form of dopamine sulfate, a compound formed by the action of the enzyme sulfotransferase 1A3/1A4 on free dopamine. The bulk of dopamine sulfate is synthesized in the mesenteric organs surrounding various parts of the digestive system. According to scientists, dopamine sulfate is synthesized according to the principle of detoxification of dopamine that enters the body with food or synthesized during digestion - after eating, the concentration of dopamine in plasma increases by more than 50 times. Having no biological function (being useless), dopamine sulfate is excreted from the body along with urine. The relatively small amount of unbound dopamine in the blood is synthesized with the participation of the sympathetic nervous system, the digestive system, and probably other organs. It acts on dopamine receptors in peripheral tissues and is metabolized or taken the form of norepinephrine (by the action of the enzyme dopamine beta-hydroxylase, which is “injected” into the bloodstream by the amygdala). Some dopamine receptors attach to the walls of arteries, where they perform a vasodilator function and block the production of norepinephrine. This type of response occurs when dopamine is released from the carotid paraganglion when oxygen levels are low, but scientists are not sure whether these receptors have other important functions. Some peripheral systems in which dopamine circulates, in addition to regulating blood circulation, perform an exocrine or paracrine function. These include:

The endocrine lobe of the pancreas, also known as the islet of Langerhans, synthesizes a number of hormones, including insulin, which are subsequently released into the blood. According to some data, beta cells that synthesize insulin contain dopamine receptors, which, in turn, prevents them from releasing insulin. Scientists still have not figured out where dopamine comes from - from the circulatory system, from the sympathetic nervous system, or whether it is synthesized in certain areas of the pancreas by its other cells.

Action of dopamine at the cellular level

Like many other biologically active substances, dopamine attaches to receptors on the surface of cells, activating those receptors. In mammals, scientists identify five types of dopamine receptors (D1-D5). All of them function as G-protein coupled receptors, that is, their activity is regulated by a system of secondary messengers. Without going into details, dopamine receptors in mammals can be roughly grouped into two families (D1-like and D2-like). The result of the activity of D1-like receptors (D1 and D5) can be both excitation (when sodium channels open) and inhibition (when potassium channels open); D2-like receptors (D2, D3 and D4) typically ultimately inhibit the targeted neuron. That is why it is incorrect to consider dopamine either only as an excitant or only as an inhibitor. It affects neurons differently, depending on what receptors are present on the membrane of each particular neuron and on the internal reaction of a particular neuron to AMP. The central nervous system has the most D1 receptors (and further in descending order). The level of extracellular dopamine depends on two factors (mechanisms): tonic and phasic transmission of dopamine. Tonic transmission begins with the release of small amounts of dopamine, independent of neuronal activity, and is regulated by the reuptake of other neurons and neurotransmitters. The phasic production of dopamine is a consequence of the activity of cells containing dopamine. This process is characterized by an irregular acceleration of the synthesis of individual “portions” (the peak potential is 2–6 rapid emissions one after another).

Substantia nigra, dopamine system and motor control

The substantia nigra is one of the components of the subcortical nuclei, a group of interconnected structures in the front and middle parts of the brain that are responsible for motor function. Scientists have not fully understood the algorithm for this function, but describe it as “response selection.” Adherents of this theory are convinced that when a person or animal has a choice (several options for action) of what to do in a given situation, the subcortical nuclei are activated, which determine the choice of one or another option. Thus, the subcortical nuclei determine our situational behavior (without affecting the details). Dopamine is thought to modulate response selection (in at least two ways). First, dopamine determines the “boundaries of effort”: the more active dopamine, the less incentives will be required to choose a particular behavior model. Consequently, high concentrations of dopamine significantly increase motor activity and provoke “impulsive” behavior; with low dopamine levels, a person, on the contrary, becomes lethargic and inhibited. In Parkinson's disease, in which dopamine reserves in the substantia nigra are almost completely depleted, numbness occurs, and movements become rare and slow, and, nevertheless, when people with this syndrome are exposed to powerful external stimuli (for example, when they feel something threatens), their reactions become timely, like healthy people. Conversely, drugs that enhance the effects of dopamine (cocaine and amphetamine) cause hyperactivity, in particular excessive psychomotor agitation and stereotypic movements. Dopamine is also a kind of irritant for the development of a reflex. The motor reflex is accompanied by an increase in dopamine activity, as a result of which the sequence of the subcortical nuclei changes (in such a way that the next time in a similar situation the desired reaction will occur faster). This process is a type of operant conditioning (learning by trial and error), with dopamine playing the role of a “rewarding” signal. Structure and physical properties The subcortical nuclei have a rather complex structure, so the role of dopamine in this case is far from ambiguous. Within the macro, the action of dopamine is projected only from the pars compacta of the substantia nigra to the striatum, but it contacts various neurons, transforming their targets (activating one part of them through D1 receptors and inhibiting the other part using D2 receptors. A significant amount of dopamine enters the necks of dendritic spines, from where it has a synchronizing effect on specific synapses originating in the cerebral cortex. There are two separate channels through which dopamine signals travel (synthesized in the striatum), namely the direct and indirect channels. It is believed that dopamine is activated when the direct channel is opened and the indirect channel is blocked. Many theorists believe that the basis for the formation of a motor skill in the subcortical nuclei is long-term potentiation of the striatum, the main regulator of which is dopamine; in other words, this is a mechanism according to which dopamine promotes either strengthening or weakening of synaptic connections within the striatum. Ventral tegmental area and “reward” The ventral tegmental area (VTA) contains the bulk of dopamine neurons (if we talk about the human brain). Their signals are projected to many areas of the brain, but most actively this occurs in the mesolimbic canal, from where the action of neurons extends to the nucleus accumbens (“pleasure center”) and other limbic structures, as well as in the mesocortical canal (“targets” of which are the prefrontal and insular areas of the prefrontal cortex. “Reward” The dopamine system of the VTA is directly related to the “reward” system of the brain. The production of dopamine in such areas as the nucleus accumbens and the prefrontal cortex is a consequence of “rewards” in the form of tasty food, sex and neutral stimuli, which are associated with them, the source of dopamine in this case is primarily the VTA, although the substantia nigra also plays a role in this process. Electrical stimulation of the VTA or its outlet channels is itself a potential “reward”: animals quickly learn to “switch the desired ones. levers” to activate dopamine synthesis and often they like it and don’t stop, gradually increasing the pace. Various medications (in particular, narcotic drugs), after taking which the level of dopamine in the blood increases sharply, in fact, are also a kind of “reward” and enhance the effect of other “rewards”. Despite extensive evidence of the close relationship between dopamine and the brain's "reward" behavior, scientists cannot agree on whether the action of dopamine (itself) is a "reward" or whether dopamine merely contributes to this complex process. The difference in opinion is due to two observations: (1) Being a “reward”, dopamine at the same time irritates the central nervous system (due to which a person cannot sit still, making various movements; (2) dopamine is often synthesized under the influence of factors that have no relationship to reward (the most striking example is pain). One of the most popular alternatives to the reward theory is the “stimulus-response” theory, whose supporters are convinced that the main function of dopamine is to enhance stimuli of various natures (both positive and negative). According to numerous studies, dopamine is not the “reward” itself, but rather its action is due to “an erroneous forecast regarding this reward, that is, it determines the degree of surprise of a particular reward. Adherents of this hypothesis, which is based on the notes of Wolfram Schultz, are sure. that if the reward was not a surprise, then dopamine is not activated, whereas in the case of a “surprise” the level of dopamine in the blood briefly increases, and in the absence of the expected reward, its concentration, on the contrary, decreases (to a level below the original). The “misprediction” hypothesis has attracted considerable interest from neuroscientists because a computational learning method known as temporal differences involves intensive use of the signal in which the misprediction is encoded. The full correspondence of the theory with the available data gave rise to closer and more fruitful collaboration between neurobiological theorists and practitioners. The results of recent studies provide clear evidence that even though some dopaminergic neurons function as “reward” neurons, others do not respond to “surprises,” particularly negative ones. In this study, scientists found that “reward” neurons predominate in the ventromedial zone of the substantia nigra pars compacta and in the ventral tegmental area. The signals from these neurons project primarily to the ventral striatum, thereby conveying valuable “reward” information. Most emotional neurons are located in the dorsolateral zone of the pars compacta of the substantia nigra, from where their signals are projected onto the dorsal striatum, thus determining the choice of one or another behavior model. Scientists hypothesize that the differences between these two types of dopaminergic neurons are due to the sources of their signals: reward signals are synthesized in the basal forebrain, while emotional (response to surprise) neurons are synthesized in the lateral frenulum of the epithalamus. In primates, neurons in the substantia nigra and VTA project their signals to the prefrontal cortex; Scientists are still puzzling over how and why dopamine innervates other areas of the primate cerebral cortex. For many years, there has been an opinion that under conditions of stress (even minor ones), the production of dopamine in the prefrontal cortex of rodents noticeably accelerates, which indicates a strong influence of emotional dopamine neurons on this area. “Striving” and “Satisfaction” (Differences) At one time, Kent Berridge and other researchers vigorously debated the difference between “reward” (from the point of view of motivation) and pleasure (through the prism of emotional expression). In simple terms, they tried to distinguish "aspiration" from "satisfaction." The desire arises in the presence of certain stimuli (for example, food), under the influence of which the animal tries to behave in such a way as to deserve (receive) this “reward”. "Satisfaction" is a feeling of happiness and pleasure, for example, while eating. Many studies suggest that the dopamine system is an integral part of the brain's drive (but not gratification) system. Drugs that increase the production and action of dopamine (mainly psycho-stimulants such as methamphetamine and cocaine) similarly increase a person's desire, but have little effect on pleasure. Conversely, opiates such as heroin and morphine increase pleasure but have little effect on craving. Animals with an inactive VPA-dopamine system will not strive to find food, even when hungry, and will continue to starve until death (unless humans intervene), however, if you put a piece of food in your mouth, they will eat it with pleasure, expressing satisfaction with everything with his appearance. Participation of dopamine in the formation of cognitive function Scientists are actively studying the influence of dopamine on the formation of higher mental activity using the example of monkeys and rodents. It all started with a study conducted by Brozoski and his team in 1979, in which scientists were able to clearly demonstrate that when catecholamines were depleted in the prefrontal cortex of monkeys, their spatial memory was impaired (in the same way as when the prefrontal cortex itself was removed). . Recently, scientists have found that both dopamine and norepinephrine have a significant effect on the functioning of the PFC, helping to coordinate cognitive function with central nervous system arousal. The role of dopamine in the formation of the function of the PFC can be clearly expressed through a U-shaped dependence curve, while, acting on its D1 receptors, dopamine to one degree or another disrupts short-term memory. In the prefrontal cortex of primates, when stimulating the D1 receptor of dopamine, they are selectively excited “delay” cells (which are also called “memory” cells), while when D2 receptors are activated, the degree of excitation of “reflex cells” changes. Pharmacology There are several commercial names (trade names) of dopamine (“Intropin”, “Dofastat”, “Revimin”, etc.), under which it is widely used both in the form of an oral drug and in the form of an injection solution. Most often, dopamine is used to treat acute forms of hypotension, bradycardia (slow heart rate), circulatory shock, or cardiac arrest, especially in newborns. The effects of dopamine depend on its dosage: it can stimulate renal excretion of sodium, increase heart rate and increase blood pressure. At a “cardio-beta” dosage (5-10 mcg/kg/min), dopamine, acting on the sympathetic nervous system, increases the frequency of contractions of the heart muscle, thereby increasing the volume of the heart and increasing blood pressure. At the “pressor alpha dosage” (10 - 20 mcg/kg/min), dopamine has a vasoconstrictor effect, which further increases blood pressure, often causing unpleasant and serious side effects such as renal failure and cardiac arrhythmia. Earlier references mention a "renal/dopaminergic dosage" of dopamine (2 - 5 mcg/kg/min) that restores (and even improves) liver function without any side effects, but recent studies have found such low dosages, in fact, are not effective (from the point of view of treating diseases) and can often only harm the body. The toxicity LD50, or the dose that is lethal in 50% of cases, for dopamine is: 59 mg/kg (in mice; by intravenous injection); 950 mg/kg (for mice; intraperitoneal injection); 163 mg/kg (for rats; intraperitoneal injection); 79 mg/kg (for dogs; intravenous). L-DOPA Levodopa is a dopamine precursor substance that is actively used (in various forms) to treat Parkinson's disease and dopamine agonist-sensitive dystonia. As a rule, this drug is taken together with a peripheral decarboxylation inhibitor (DDC, dopa decarboxylase), marketed under the trade names “carbidopa” and “benserazide”. In some cases, levodopa is combined with inhibitors of alternative dopamine metabolic channels (catechol-O-methyl-transferase); in the form of entacapone and tolcapone). Psychostimulants Cocaine and amphetamines increase the activity of dopamine neurons; and yet their mechanisms are very different. Cocaine is a dopamine transporter and norepinephrine transporter blocker. It is a non-competitive inhibitor of dopamine reuptake (resulting in increased dopamine levels in the synaptic cleft). Like cocaine, analogue amphetamines increase the influx of dopamine into the synaptic cleft, but their mode of action is much more complex than that of cocaine. Amphetamine enters presynaptic neurons through the neuronal membrane or DAT, after which (once inside) it attaches to the TAAR1 receptor or enters synaptic vesicles through VMAP-2. When amphetamine enters synaptic vesicles via VMAT2, dopamine is released into the cytosol. By binding to TAAR1, amphetamine reduces dopamine receptor firing rate (via potassium channels) and activates protein kinase A (PKA) and protein kinase C (PKC), causing DAT to be phosphorylated. When the phosphorylator of DAT is PKA, DAT flows back into the presynaptic neuron (absorbed by it), stopping further movement. If PKS acts as a phosphorylator, then two scenarios for the “behavior” of DAT are possible (the scenario opposite to the one described above and PKS). As is known, amphetamine also increases the influx of calcium into cells (due to activation of the TAAR1 receptor), which is associated with phosphorylation of DAT (within the CAMK kinase channel), against which the outflow of dopamine from cells occurs.

Antipsychotics Certain drugs that reduce dopamine activity have been successfully used to treat schizophrenia and other mental disorders. These antipsychotic medications, also known as antipsychotics or "major tranquilizers," are different from "mild tranquilizers" (such as Valium), which are used to relieve anxiety and treat insomnia. Neuroleptics suppress almost any type of activity, in particular, they effectively cope with inappropriate behavior (delusional ideas) and increased psychomotor activity (a typical sign of psychosis). With the advent of the first universal antipsychotic drug chlorpromazine (Thorazine) in the 50s, many schizophrenics switched to outpatient treatment (that is, they were discharged from mental health centers). And yet, for a long time, antipsychotics were under the suspicion of scientists, and there are several reasons for this. Firstly, many people develop persistent aversions (for example, to food, alcohol, etc.) while taking antipsychotics, since they dull thinking, make a person inhibited, and deprive him of the ability to experience pleasure. Secondly, it has not yet been proven that their action is aimed specifically at combating psychotic behavior, and not at suppressing any kind of activity. Third, antipsychotics are often associated with serious side effects, including weight gain, diabetes, fatigue, sexual dysfunction, hormonal imbalances, and tardive dyskinesia (a type of movement disorder). Some side effects do not disappear even after stopping the drug (and in some cases, they “torment” the person for the rest of his life). The earliest antipsychotics (developed specifically to treat psychosis) strongly interfered with many of the functions of dopamine. Such drugs are called “typical antipsychotics.” Due to the severe side effects of these drugs, scientists began to develop a new generation of antipsychotics, which they called “atypical antipsychotics” or “new generation antipsychotics”; These drugs act only on certain dopamine receptors that are directly related to the development of psychosis, thereby relieving psychotic symptoms, but do not cause such serious side effects. And yet, the new generation of antipsychotics has become the subject of heated debate, since many scientists and doctors doubt that these drugs really improve the condition of patients (some believe that they have a weak effect). Various Diseases and Disorders The dopamine system plays a key role in the development of certain diseases and disorders, including Parkinson's disease, attention deficit hyperactivity disorder, schizophrenia and drug addiction. Parkinson's disease Parkinson's disease is a disorder in which a person develops rigidity (he becomes inactive, often in a daze), movements slow down and limbs begin to tremble involuntarily. In later stages, this disease often develops into dementia, and ultimately leads to death. The main symptoms of Parkinson's disease arise from a significant depletion of dopamine-synthesizing cells in the substantia nigra. These cells are the most fragile and are destroyed faster than others, which is facilitated by various brain injuries, including encephalitis (which is described in the book and film of the same name “Awakening”), contusions and concussions in athletes, and certain forms of poisoning (for example, MPTH), which are accompanied by a strong decrease in the level of cells that synthesize dopamine, as a result of which a person develops Parkinson's syndrome, which is almost completely identical to Parkinson's disease. And yet, in most cases, Parkinson's disease has an “idiopathic” basis (that is, the cause of cell death has not been established). L-DOPA, a metabolic precursor of dopamine, is most often used to treat Parkinson's disease. This treatment method does not allow replenishing depleted cell reserves, but forces the remaining cells to more actively synthesize dopamine, thereby partially compensating for losses. In the later stages of the disease, this type of treatment loses its effectiveness because there are so few cells that they cannot synthesize enough dopamine (regardless of the dose of L-DOPA taken). With the onset of the late stage of Parkinson's disease, the mechanisms that regulate the metabolism of dopamine cells are disrupted, becoming chaotic, as a result of which a person develops dopamine dysregulation syndrome, when the patient's condition constantly fluctuates (hyperactivity is replaced by paralysis and vice versa). Attention Deficit Hyperactivity Disorder When the speed of dopamine neurotransmission changes, a person develops attention deficit hyperactivity disorder (ADHD), a disease that is accompanied by the inability to concentrate on something, inattention and/or impulsivity. There is some relationship between dopamine receptors, its transporters and ADHD at the genetic level. This connection is most clearly evident when taking medications aimed at treating ADHD. The most effective drugs in this case are psychostimulants such as methylphenidate (Ritalin, Concerta) and amphetamine (as these drugs increase the levels of dopamine and norepinephrine in the brain). Drug addiction When drug addiction develops (from a particular drug or drug), gene expression changes in the nucleus accumbens, which, in turn, affects the neurotransmission of dopamine. The most important transcription factors responsible for these changes are ΔFosB, cyclic adenosine monophosphate (cAMP), cAMP response element activating protein (CREB), and nuclear factor kappa bi (NFκB). The most significant factor is ΔFosB, since it is its “reserves” (large) in the nucleus accumbens that are necessary for the manifestation of most adaptive reactions of the brain in drug addiction; This factor is responsible for the development of addiction to many drugs, including cannabinoids, cocaine, nicotine, phenylcyclidine and analog amphetamines. The transcription factor ΔJunD is a direct antagonist of ΔFosB. When the level of ΔJunD in the nucleus accumbens increases, adaptive addictive reactions of the brain (which are observed in chronic drug addiction) partially or completely disappear (the ΔFosB factor blocks them). Moreover, ΔFosB regulates behavioral responses to natural “rewards” of the brain (tasty and pleasant-smelling food, sex and exercise). Since natural “rewards”, like drugs, induce the ΔFosB factor, when such “rewards” are regularly received, a person gets used to them and needs more and more of them (to satisfy his needs). ΔFosB inhibitors (drugs that block this factor) are successfully used to treat drug addiction and related disorders. Pain Scientists have shown that dopamine is involved in processes associated with pain at various levels of the central nervous system, including the spinal cord, periaqueductal gray matter (APG), thalamus optic, subcortical nuclei and anterior cingulate cortex. Consequently, when dopamine levels decrease, pain occurs (this often occurs against the background of Parkinson's disease). Abnormalities in dopaminergic transmission are characteristic of such discomforting diseases as neurogenic glossitis (burning mouth syndrome), fibromyalgia and restless legs syndrome. In general, the analgesic effect of dopamine is due to activation of the D2 receptor; the exception is the OPSV zone, where, upon activation, pain sensations attenuate upon activation of the D1 receptor, which is apparently associated with the excitation of neurons that participate in “descending inhibition.” Moreover, when the D1 receptor is activated in the insular region of the cerebral cortex, subsequent pain sensations become less pronounced. Nausea Nausea and vomiting are largely related to processes in the brain stem known as the chemoreceptor trigger zone. It contains a large group of D2 receptors. Consequently, drugs that activate these receptors cause severe nausea. These include drugs used to treat Parkinson's disease, as well as other dopamine agonists such as apomorphine. D2 receptor antagonists (eg, metoclopramide) are often effective in relieving nausea. Psychosis Overactive dopaminergic transmission is a symptom of psychosis and schizophrenia. However, evidence from clinical studies linking schizophrenia to impaired dopamine metabolism in the brain varies greatly (from controversial to negative), since the concentration of HVA in the cerebrospinal fluid was found to be similar in both schizophrenics and healthy controls. groups. Schizophrenics exhibit increased dopaminergic activity, particularly in the mesolimbic channel. And yet, this is often accompanied by a decrease in dopamine activity in another (mesocortical) channel. It is generally accepted that both channels are responsible for various symptoms of schizophrenia. Neuroleptics, for the most part, act on the principle of antagonism towards dopamine, inhibiting it at the receptor level and thereby blocking the neurochemical effect in proportion to the dosage. Most of the older generation of antipsychotics, the so-called "typical antipsychotics", act on the D2 receptors, while the action of the "atypical antipsychotics" is also directed at other receptors (D1, D3 and D4), although they have less affinity for the dopamine receptors themselves . The discovery of the ability of drugs like amphetamines, methamphetamine and cocaine to increase dopamine levels by more than 10 times, thereby causing temporary psychosis, is further evidence of this. And yet, many drugs that have nothing to do with dopamine can also cause both acute and chronic psychosis. NMDA receptor antagonists (ketamine and PCP) are being actively studied in attempts to recreate the positive and negative symptoms of schizophrenia. Dopaminergic dysregulation is also observed in depressive disorders. In the past, scientists have extensively studied the relationship between the levels of dopamine in the blood of people suffering from depression and depression itself. In numerous studies, scientists have concluded that depressed people have lower levels of tyrosine (a dopamine precursor substance) in plasma, ventricular and lumbar spinal fluid than healthy people (control group). The authors of one such experiment measured the level of homovanillic acid (the main metabolite of dopamine in the cerebrospinal fluid) in people suffering from depression. Scientists often use reverse transcriptase polymerase chain reaction (RT-PCR) to detect gene expression in specific dopamine receptors in the amygdala; this indicator tends to be elevated in people suffering from depression compared to healthy people. The principle of action of popular antidepressants is also based on the transformation of dopaminergic channels. Many antidepressants cause an increase in extracellular dopamine concentrations in the prefrontal cortex of rats, but the effects of these drugs on the striatum and nucleus accumbens vary widely, the scientists said. This can be compared to electroconvulsive therapy (ECT), which increases dopamine levels in the striatum of rats by hundreds of times. In later experiments with rodents, scientists noticed that depressive behavior patterns were associated with malfunctions of the dopaminergic system. Rodents exposed to mild chronic stress have a less developed avoidance (danger) response and show worse results in the forced swim test, which is associated with activation of the dopaminergic mesolimbic channel. In addition, depressive behavior in rodents is often a consequence of lack of recognition in “society” and can change for the better with the activation of dopaminergic channels. Moreover, science knows cases of dopamine splitting in the caudate and accumbens nuclei against the background of acquired helplessness in animals. The first symptoms are relieved by dopamine agonists and antidepressants, provided that the animal has not yet become helpless. Applied biology and evolution Microorganisms Scientists have not discovered dopamine in archaea, but some other bacteria and ciliates from the genus Tetrahymena can synthesize it. Most importantly, some bacteria contain homologues of all the enzymes that animals use to synthesize dopamine. Scientists suggest that animals synthesize dopamine with the help of bacteria, through horizontal gene transfer (this occurred at a fairly late stage of evolution, and was probably due to the symbiosis of bacteria with eukaryotic cells that form mitochondria. Animals Almost all multicellular animals use dopamine for " communication" between cells. Science knows of only one case of the detection of dopamine in spongiosa (sponges), and its function has not been established; And yet, scientists have found dopamine in the nervous systems of many species with radial symmetry, including cnidarians (jellyfish, hydra, corals, etc.). All this indicates that dopamine from time immemorial (more than 500 million years ago, back in the Cambrian period of the Paleozoic era) served as a neurotransmitter in the nervous system of living organisms, in particular, vertebrates, echinoderms, arthropods, mollusks and some types of worms. In all animals, dopamine affects motor skills. In the well-studied nematode worm Caenorhabditis elegans, dopamine slows locomotion and promotes more active foraging. In planarians, dopamine causes “helical” movements; it deprives leeches of the ability to swim, forcing them to crawl; etc. In many vertebrates, dopamine activates the “functions” of switching behavior patterns and selecting a response (as in mammals). Additionally, dopamine is an integral part of the brain's reward system (in all animals except arthropods), and recent research has shown that dopamine is (at a minimum) a reward mediator in the fruit fly. Nematodes, planarians, mollusks, black-bellied fruit flies and vertebrates can be trained to produce dopamine. For a long time it was (and is) believed that arthropods are an exception to this rule, since in representatives of this class (insects, crustaceans, etc.) dopamine causes the opposite effect, and the mediator of the “reward” system in them is octopamine (a neurotransmitter that is absent in vertebrates, but in its structure and properties resembles norepinephrine). According to some data, octopamine’s ability to increase appetite is due to the activation of a group of dopaminergic neurons that previously simply could not be “reached.” An independent population of dopamine-synthesizing cells contributes to increased aversion caused by the olfactory response to odors (the same thing happens in mammals). Plants Many plants (in particular, edible ones) are, to one degree or another, capable of synthesizing dopamine. The most dopamine is found in bananas (in the pulp of red and yellow bananas, the concentration of dopamine is 40-50 ppm of the mass of the fruit itself. Potatoes, avocados, broccoli and Brussels sprouts may also contain dopamine (1 ppm or more); in oranges, tomatoes , spinach, beans, etc. – less than 1 millionth. In plants, dopamine is synthesized from the amino acid tyrosine (in a similar way as in animals). Dopamine is metabolized in several ways (melanin and various alkaloids are by-products of this reaction). The functions of plant catecholamines have been little studied, but scientists have proven that they play a certain role in shaping the response of plants to external stress factors, such as bacterial infection, in some cases they play the role of a kind of “growth hormone” and make certain changes in the metabolism of sugars . Dopamine, which enters the body with food, cannot affect the brain, being unable to cross the blood-brain barrier. And yet, many plants contain L-DOPA, a metabolic precursor of dopamine. Most of it is in the leaves and pods of plants from the genus Mucuna, especially Mucuna pungent (velvet beans), which is a medicinal product and a valuable source of L-DOPA. Another plant rich in L-DOPA is the common bean, from which fava beans (also known as “green beans”) are derived. Yet the concentration of L-DOPA in the beans themselves is much lower than in the pod skin and other parts of the plant. The seeds of the Cassia and Bauhinia shrubs also contain significant amounts of L-DOPA. The yellowish-green seaweed Ulvaria dura, which is the main “component” of water blooms, is very rich in dopamine (approx. 4.4% dry weight). Scientists have proven that dopamine in this algae protects it from being eaten by marine herbivores (snakes and isopods). Melanin precursor substance Melanins are a group of dark-colored substances found in many living organisms. Due to the physical properties of melanins, experiments with them are carried out extremely rarely (it is very difficult), therefore certain aspects of their biochemistry are poorly understood and are a “mystery” for scientists. They are very similar in chemical composition to dopamine, and there is a specific type of melanin known as “dopamine-melanin”, which is synthesized by the oxidation of dopamine with the participation of the enzyme tyrosinase. Melanin, which is responsible for the dark shade of human skin, is of a different type: it is synthesized in a channel in which L-DOPA, rather than dopamine, acts as a precursor substance. And, nevertheless, there is a lot of evidence that all the “neuro-melanin” that gives the dark color to the substantia nigra of the brain is at least partially composed of “dopamine-melanin”. Melanin, derived from dopamine, is likely present in at least a few other biological systems. Part of plant dopamine is a precursor of “dopamine-melanin”. The complex segments on the wings of butterflies, as well as the black and white stripes on insect larvae, are thought to be the result of accumulations of “dopamine-melanin.” Mechanisms of biochemical reactions According to its structure, dopamine belongs to the classes of catecholamines and phenethylamines. As part of the biological system, dopamine is synthesized in brain and adrenal cells from L-DOPA. In brain cells, it combines with receptors, after which it is released in the form of bubbles (synoptic transmission). After this, dopamine is either resorbed in the presynaptic terminal (for secondary use) or is broken down by the enzymes monoamine oxidase or COMT into various metabolites. Biosynthesis Dopamine is not synthesized in all cells, most often in neurons and cells of the adrenal medulla. Below is the metabolic pathway of dopamine: L-phenylalanine → L-tyrosine → L-DOPA → dopamine As we can see, the direct “precursor” of dopamine is L-DOPA, but dopamine can be synthesized without the participation of its precursor: from the essential amino acids phenylalanine and tyrosine. These amino acids are found in almost all protein foods (tyrosine is more common). Despite the fact that dopamine itself is found in many foods, it is not able to cross the blood-brain barrier that protects our brain. Only dopamine, which is synthesized inside the brain, is able to affect the central nervous system. L-phenylalanine takes the form of L-tyrosine (with the participation of the enzyme phenylalanine hydroxylase (PAH) and associated factors - oxygen (O2) and tetra-hydro-bioprotein (THBB). In turn, L-tyrosine is converted into L-DOPA (under by the action of the enzyme tyrosine hydroxylase (TH) and associated factors - tetrahydro-bioprotein (THBP), O2 and ferrous iron (Fe2+), as a result, with the participation of the enzyme aromatic L-amino acid decarboxylase (DALA; also known as DOPA decarboxylase (). DDC) and the accompanying factor pyridoxal phosphate (PLP), L-DOPA takes the form of dopamine. Dopamine itself often acts as a precursor in the synthesis of neurotransmitters - norepinephrine and epinephrine under the action of the enzyme dopamine-β-hydroxylase (DBH) and related factors (O2). and L-ascorbic acid), dopamine takes the form of norepinephrine, which in turn is converted to epinephrine (with the participation of the enzyme phenyl-ethanolamine-N-methyl-transferase (PHMT) and the accompanying factor - S-adenosyl-L-methionine (SAM )). It should be noted that some accompanying factors themselves must be synthesized before entering the reaction. In the absence (or deficiency) of any of the necessary amino acids or one or another associated factor, the subsequent biosynthesis of dopamine, norepinephrine and epinephrine is disrupted. Storage, Secretion, and Reuptake Inside the brain, dopamine functions as a neurotransmitter that operates in many ways similar to other neurotransmitters. Newly synthesized dopamine is transferred from the cytosol to the synoptic vesicles (in which it is assisted by the vesicular monoamine transporter-2 (VMAP-2). Dopamine continues to accumulate in these vesicles until they push it into the synoptic cleft in one of the following two ways: how As a rule, the vesicular action potential “forces” the vesicles to get rid of their contents, which are directly “catapulted” into the synaptic cleft (scientists call this process exocytosis or extracellular process); however, sometimes dopamine neurons, being colocalized with the TAAR1 receptor, release dopamine into the synapse, similarly. amphetamine in the presence of the required amount of endogenous phenethylamine. Once in the synapse, dopamine attaches to dopamine receptors, activating them; these receptors are concentrated either in the post-synaptic target cells or on the membrane of the pre-synaptic cell from which dopamine is released (for example, short ones). auto-receptors D2). After the action potential has been “triggered,” dopamine molecules are immediately detached from their receptors, after which they are again absorbed by the pre-synaptic cell through reuptake, the mediator of which is either a high-affinity dopamine transporter (DAP) or a low-affinity monoamine one. plasma membrane transporter (PMAP). Once in the cytosol, dopamine is reintroduced into the vesicles (with the participation of VMAP-2), which ensures its further movement. Breakdown Dopamine breaks down into inactive metabolites, in which it is helped by a complex of enzymes: monoamine oxidase (MAO), aldehyde dehydrogenase (ALDH) and catechol-O-methyl-transferase (KOMT), acting one after the other. The iso-forms of MAO, MAO-A and MAO-B are equally effective in this case. Metabolites: DOPAL (3,4-dihydroxy-phenyl-acetate-aldehyde) DOPAC (3,4-dihydroxy-phenyl-acetic acid) DOPET (3,4-dihydroxy-phenyl-ethanol, also known as hydroxy-tyrosol) MOFET ( 3-methoxy-4-hydroxy-phenyl-ethanol, also known as homovanillyl alcohol) 3-MT (3-methoxy-tyramine, partial agonist of the TAAR1 receptor) HVA (homo-vanillic acid) All of these metabolites are reaction intermediates except MOFET and HVA, which are filtered by the kidneys from the circulatory system and then excreted from the body along with urine. Specific metabolic reactions: Dopamine → DOPHAL (mediator - MAO) DOPHAL → DOPAC (mediator - ADGG) DOPHAL → DOPHET (mediator - aldose reductase (auxiliary excretion pathway) DOPAC → GVK (mediator - COMT) DOPHET → MOFET (mediator - COMT) Dopamine → 3-MT (COMT) 3-MT → HVA (MAO) In most areas of the brain, including the striatum and subcortical nuclei, dopamine is deactivated by reuptake from the dopamine transporter (DAT), after which dopamine is degraded under the influence of MAO, converted to DOPAC. However, there are too few DAT proteins in the prefrontal cortex, and therefore dopamine is deactivated by reuptake from the norepinephrine transporter (NET), most likely in the vicinity of norepinephrine neurons, after which dopamine is broken down to state 3-MT (under the influence of COMT). DAT is a faster and more active transporter than NET: in mice, dopamine levels in the blood gradually decrease, with a half-life of 200 milliseconds from the caudate nucleus (excretion pathway - DAT) and 2,000 milliseconds. in PFC. Unsplit dopamine takes the form of bubbles (which is necessary for further movement). Chemical Properties From a chemical point of view, the dopamine molecule consists of a catechin structure (a benzene ring with two hydroxyl groups on the sides) to which one amine group is attached. By itself, dopamine is the simplest catecholamine in existence (a family that also includes the neurotransmitters norepinephrine and epinephrine). In the presence of a benzene ring with attached amines, phenethylamine is formed (numerous psychostimulants belong to this family). Like most amines, dopamine has an organic base. At neutral or acidic pH, protons tend to attach to dopamine. Protonated dopamine is highly soluble in water and has a fairly dense structure, although it is oxidized under the influence of oxygen or other oxidants. At alkaline pH, dopamine loses protons. In its alkaline form, dopamine is less soluble in water, highly reactive, and easily oxidized. Being pH-sensitive, the chemical and medicinal dopamine is in the form of dopamine hydrochloride, that is, it is produced in the form of a hydrochloride salt, which is formed when dopamine combines with hydrochloric acid. Dry dopamine hydrochloride is a colorless powder with small granules. After dissolution in distilled water, a moderately acidic and dense solution is obtained. However, dopamine is not combined with alkaline electrolytes, such as bicarbonate buffer solution, since in this combination it (dopamine) loses its properties (deactivated). Oxidation Once in the body, dopamine, as a rule, decomposes during the oxidation process (the enzyme monoamine oxidase acts as a catalyst. And, nevertheless, dopamine has the ability to self-oxidize, that is, it directly reacts with oxygen, resulting in the formation quinones and various free radicals (reaction by-products). In the presence of ferrous iron and other factors, auto-oxidation occurs faster. The ability of dopamine to auto-oxidize with the subsequent synthesis of quinones and free radicals makes it a powerful cellular toxin, moreover, scientists have proven that this mechanism of action. dopamine causes loss of cell sensitivity (as in Parkinson's disease and some other diseases). Poly-dopamine During an experiment with shellfish adhesive proteins (2007), scientists discovered that many materials, if placed in a slightly alkaline solution of dopamine, become coated. a layer of polymerized dopamine, which is often called poly-dopamine. Polymerized dopamine undergoes a spontaneous oxidation reaction, and, in fact, is a type of melanin. Synthesis usually involves the reaction of dopamine with trometamol (as an alkali) in water. The structure of poly-dopamine has been studied very little. Poly-dopamine coating forms on the surface of objects of various sizes, ranging from nanoparticles to large surfaces. Scientists are actively studying the properties and potential applications of such a coating, and are convinced that it can soon be used to protect objects and substances from destruction under the influence of light or for the production of drug shells (capsules). In more sophisticated applications, polydopamine could be used as a substrate for biosensors and other biologically active macromolecules. History Dopamine was first synthesized in 1910 by George Barger and James Evens at the Wellcome Laboratory in London (England); in 1957, Kathleen Montagu first discovered dopamine in the human brain. Dopamine got its name from being a monoamine, the precursor of which (during the Barger-Evens synthesis) was 3,4-dihydro-phenylalanine (levodopamine or L-DOPA). The neurotransmitter function of dopamine was discovered in 1958 by Arvid Carlson and Nils-Eik Hillarp in the chemical and pharmacological laboratory of the National Heart Institute in Sweden. In 2000, Carlsson received the Noble Prize for his achievements in the field of physiology and medicine, proving that dopamine is not just a precursor to norepinephrine (norepinephrine) and epinephrine (adrenaline), but also a neurotransmitter.

Dopamine: instructions for use and reviews

Latin name: Dopamine

ATX code: C01CA04

Active ingredient: dopamine

Manufacturer: Darnitsa (Ukraine), Armavir biofactory, EcoPharmPlus CJSC, Altair LLC, Bryntsalov-A CJSC (Russia)

Updating the description and photo: 25.01.2018

In the life of every person, sometimes there come moments when the mood rapidly deteriorates, the desire to communicate with someone disappears, and pessimistic views dominate. Experts call one of the main reasons for this condition a lack of dopamine, a hormone whose level can be regulated. That is, a bad mood can be overcome, the main thing is to know how, and not to overdo it.

Dopamine is a hormone responsible for a person’s psycho-emotional state. It supports the functioning of the heart and brain, helps control weight and is responsible for performance. The lack of this hormone in the human body leads to a constant state of depression and the accumulation of excess weight.

Decreased dopamine levels

Many people who suffer from mood swings may not even know that dopamine exists. What is it and what are the symptoms of its deficiency in the body?

A reduced level of this hormone in the body can lead to unpleasant consequences that will affect both psycho-emotional and physical health.

Lack of dopamine provokes metabolic problems that lead to obesity. The patient's behavior often exhibits inexplicable irritability, apathy, depression, and even pathological aggressiveness. People suffering from a lack of dopamine are prone to diseases such as diabetes, anhedonia, dyskinesia, Parkinson's disease, as well as disorders in the functioning of the cardiovascular system. In addition, these people suffer from decreased sexual desire, chronic fatigue, and hallucinations.

Dopamine plays a very important role in the body, and its deficiency affects both the condition of the patient and the condition of his immediate environment. In this situation, the main thing is to react in time and seek help from specialists.

Increased dopamine levels

You can very easily get rid of a lack of this hormone. For this purpose, both drugs and traditional medicine are used. It is important in this matter to start eating right, because a lot depends on the daily diet. It is worth including foods that are rich in tyrosine. They synthesize dopamine and help it be absorbed in the body. These products include fruits and vegetables (banana, apples, beets, nettles), ginseng, eggs, green tea, seafood, fish. Dopamine (what it is, discussed above) is perfectly absorbed and immediately begins to perform its inherent functions. In addition, there are nutritional supplements based on medicinal plants that also have a beneficial effect on hormone production.

Dopamine in foods

By including in your diet foods that have a positive effect on the production of the pleasure hormone, you can protect yourself from unnecessary problems at the hormonal and emotional levels. In addition to being healthy, they are also delicious, which will bring additional satisfaction. Here we are talking, first of all, about products that contain tyrosine. These include: seafood rich in Omega-3 fatty acids, eggs with a lot of tyrosine, beets with antidepressant properties, kale with folic acid, apples, bananas, good for overcoming depression, strawberries, green tea.

Increasing dopamine levels with herbs

In many cases, the lack of dopamine in the body can be combated using traditional medicine, because nature itself heals. The main thing is to know what and how. In addition, herbs have an excellent effect on humans, having a calming and relaxing effect. Such plants include ginseng, which helps improve memory and vision, and dandelion, which has a laxative, sedative, and diuretic effect. Particular attention should be paid to ginkgo biloba. Due to its complex chemical composition, dopamine is found in the plant in its pure form. Nettle also has a positive effect on dopamine levels. It can be added to salads, brewed pure or prepared as infusions.

The role of exercise

Regular physical activity has a positive effect on normalizing and maintaining the level of pleasure hormone in the body. In addition to feeling great and in a good mood, she will also give you a beautiful, slender body. With the help of sports activities, the level of not only dopamine, but also serotonin increases. Therefore, walking, jogging or cycling will help relieve stress, depression or just a bad mood.

Folk remedies that increase the level of this hormone include regular sex. By the way, affection and falling in love also have a positive effect on the production of dopamine. This is due to pleasant impressions, positive emotions, and increased heart rate. It is because of this that a person in love feels joyful and happy.

The influence of bad habits

Drugs, alcohol and smoking negatively affect the condition of the entire human body. But, unfortunately, these bad habits are now very common and are affecting more and more people every day. They can interfere with the normal production of dopamine, and the impression of satisfaction after taking them is false and fleeting. The feeling of pleasure received after the next dose is the main reason for the development of addiction.

A reduced level of dopamine can develop due to the systematic consumption of foods that contain food. Do not get carried away with coffee, because caffeine also reduces the level of the hormone of happiness, which can result in an unstable emotional state, poor health, problems with the heart and kidneys. Giving up bad habits is the key to a good mood, excellent health and good health.

What drugs affect dopamine levels in the body?

Low levels can also be increased with the help of drugs that contain dopamine (a hormone). These are, as a rule, food supplements that have no side effects and only have a positive effect on the body’s condition.

Drugs that increase the level of pleasure hormone in the body include products containing phenylalanine. The action is aimed at converting tyrosine and synthesizing it into dopamine. What is tyrosine? An amino acid that is part of proteins and has a positive effect on the production of happiness hormones. It turns into dopamine. The use of phenylalanine must be discussed with your doctor.

Natural herbal remedies that increase dopamine levels include ginkgo biloba. The substance affects blood supply and brain function, and also ensures normal transmission of nerve impulses.

Neurologists and therapists are often asked questions about how to increase dopamine in the body. Very often, doctors prescribe antidepressants. But any specialist will emphasize that you can cope with a bad mood with proper nutrition and regular moderate physical activity.

The drug "Dopamine". Instructions

On the shelves of pharmacies you can also see the drug of the same name "Dopamine", a precursor to the biosynthesis of norepinephrine. The action of the drug is aimed at stimulating dopamine receptors. In large doses, it can also stimulate alpha and beta adrenergic receptors. The drug helps to increase total peripheral vascular resistance, increase heart contractions, and increase cardiac output. The heart rate changes little. As a result of the drug's action, coronary blood flow increases, which ensures increased oxygen delivery to the myocardium. Dopamine increases glomerular filtration and decreases renal vascular resistance. In low doses, the drug dilates blood vessels (coronary, cerebral and mesenteric), promotes the removal of sodium from the body, increases glomerular filtration and diuresis. In order to start taking this remedy, you need to consult a doctor.

Indications for use

It is definitely impossible to spontaneously and independently start using such a drug as Dopamine. What is it, how to use it and in what cases? Clear clinical reasons are needed to use this drug. The most common are shock conditions. This can be postoperative, endotoxic, traumatic, hypovolemic, cardiogenic shock. In comparison with similar drugs (catecholamines, norepinephrine), dopamine has a lesser effect on the state of peripheral vascular resistance. The drug is also indicated for acute cardiac or vascular failure. In this case, it is used to improve hemodynamics in a pathological condition.

Contraindications

There is a list of cases when the use of the drug is contraindicated, and the effect of dopamine can cause adverse reactions. Firstly, these are pregnancy and lactation, angle-closure glaucoma, heart problems (arrhythmia, severe aortic stenosis, obstructive cardiomyopathy, pericarditis. It is also not recommended to use the drug if you are hypersensitive to its components, with hyperthyroidism, with pheochromocytoma and with prostatic hyperplasia.

You should not use the product without a doctor’s prescription, because this is first and foremost a medicinal product, which, like any other, has its own indications for use.

Side effects

Despite the benefits of the drug, the effects of dopamine can also be negative. Such cases occur in case of overdose, if the patient did not listen to the doctor’s recommendations, or if he has increased sensitivity to the components of the medication. You need to carefully familiarize yourself with the properties of the drug "Dopamine". Instructions are included with each pack, so all you have to do is read it.

Side effects can be in the form of high blood pressure, arrhythmia, chest pain, tachycardia. Vomiting, nausea, anxiety, and headache may also occur. Impaired consciousness is common. Those patients who suffer from bronchial asthma may develop shock. If the drug gets under the skin, necrosis may develop. If the product gets on your skin, wash the area with soap and water.

If you experience one of the reactions listed above after taking the drug, immediately seek qualified help.

Neurotransmitter

Feeling of satisfaction

Dopamine is one of the chemical factors of internal reinforcement (ERC) and serves as an important part of the “reward system” of the brain, as it causes a feeling of pleasure (or satisfaction), which affects the processes of motivation and learning. Dopamine is naturally produced in large quantities during a subjectively positive experience - for example, sex, eating delicious food, pleasant bodily sensations. Neurobiological experiments have shown that even memories of reward can increase dopamine levels, so this neurotransmitter is used by the brain for evaluation and motivation, reinforcing actions important for survival and procreation.

Feeling of love and affection

Cognitive functions

Dopamine plays an important role in ensuring cognitive activity. Activation of dopaminergic transmission is necessary during the processes of switching a person’s attention from one stage of cognitive activity to another. Thus, insufficiency of dopaminergic transmission leads to increased inertia of the patient, which is clinically manifested by slowness of cognitive processes (bradyphrenia) and perseverations. These disorders are the most typical cognitive symptoms of diseases with dopaminergic deficiency - for example, Parkinson's disease. Dopamine is involved in learning processes; as German neuroscientists (Klein et al., 2007) showed in an experiment on humans, dopamine provides the ability to effectively learn from one’s mistakes, and a lack of dopamine can lead to ignoring negative experiences: 208-209.

Synthetic analogues. Effect of drugs on dopamine levels

Like most neurotransmitters, dopamine has synthetic analogues, as well as stimulators of its release in the brain. In particular, many drugs increase the production and release of dopamine in the brain by 5-10 times, allowing people who use them to experience feelings of pleasure in an artificial way. Thus, amphetamine directly stimulates the release of dopamine, affecting its transport mechanism. Other drugs, such as cocaine and some other psychostimulants, block the natural mechanisms of dopamine reuptake, increasing its concentration in the synaptic space. Morphine and nicotine mimic the action of natural neurotransmitters, while alcohol blocks the action of dopamine antagonists. If the patient continues to overstimulate their reward system, the brain gradually adapts to the artificially increased dopamine levels by producing less of the hormone and reducing the number of receptors in the reward system. This is one of the factors that encourages a drug addict to increase the dose to get the same effect. Further development of chemical tolerance can gradually lead to metabolic disturbances in the brain, and in the long term, potentially cause serious damage to brain health.

Biosynthesis

The precursor to dopamine is L-tyrosine (it is synthesized from phenylalanine), which is hydroxylated by the enzyme tyrosine hydroxylase to form L-DOPA, which in turn is decarboxylated by the enzyme L-DOPA decarboxylase and converted to dopamine. This process occurs in the cytoplasm of the neuron.

Receptors

Postsynaptic dopamine receptors belong to the GPCR family. There are at least five different dopamine receptor subtypes - D 1-5. The D1 and D5 receptors have quite significant homology and are associated with the GS protein, which stimulates adenylate cyclase, as a result of which they are usually considered together as D1-like receptors. The remaining receptors of the subfamily are similar to D2 and are associated with the Gi protein, which inhibits adenylate cyclase, as a result of which they are combined under the general name D-2-like receptors. Thus, dopamine receptors play the role of modulators of long-term potentiation.

D 2 and D 4 receptors take part in “internal reinforcement”.

In high concentrations, dopamine also stimulates α- and β-adrenergic receptors. The effect on adrenergic receptors is associated not so much with direct stimulation of adrenergic receptors, but with the ability of dopamine to release norepinephrine from granular presynaptic depots, that is, to have an indirect adrenomimetic effect.

"Cycle" of dopamine

Participation in the reward system

Olds and Milner's study on rats

In a seminal 1954 study, Canadian scientists James Olds and his colleague Peter Milner found that if electrodes were implanted in specific areas of the brain, especially the midforebrain ganglion, rats could be trained to press a lever in a cage that triggered low-voltage electrical stimulation. Once the rats learned to stimulate this area, they pressed the lever up to a thousand times per hour. This gave reason to assume that the pleasure center is stimulated. One of the main pathways for the transmission of nerve impulses in this part of the brain is dopamine, so researchers have put forward the theory that the main chemical associated with pleasure is dopamine. This assumption was later confirmed by radionuclide tomographic scanners and the discovery of antipsychotics (medicines that suppress the productive symptoms of schizophrenia).

Schultz's monkey experiment

Dopaminergic system

There are several known dopamine nuclei located in the brain. This is an arcuate nucleus (lat. nucleus arcuatus), giving its processes to the median eminence of the hypothalamus. Dopamine neurons of the substantia nigra send axons to the striatum (caudate and lenticular nuclei). Neurons located in the ventral tegmental area give projections to limbic structures and cortex.

The main dopamine pathways are:

• mesocortical pathway (motivational processes and emotional reactions)
• mesolimbic pathway (producing feelings of pleasure, reward and desire)
• nigrostriatal pathway (motor activity, extrapyramidal system)

Neuron cell bodies nigrostriatal, mesocortical And mesolimbic tracts form a complex of neurons of the substantia nigra and the ventral tegmental field. The axons of these neurons first run as part of one large tract (the medial forebrain bundle), and then diverge into various brain structures. Some authors combine the mesocortical and mesolimbic subsystems into a single system, but it is more reasonable to distinguish the mesocortical and mesolimbic subsystems according to projections to the frontal cortex and limbic structures of the brain.

In the extrapyramidal system, dopamine plays the role of a stimulating neurotransmitter, helping to increase motor activity, reduce motor retardation and stiffness, and reduce muscle hypertonicity. The physiological antagonists of dopamine in the extrapyramidal system are acetylcholine and GABA.

A region of the brain called the substantia nigra (substantia nigra) is a critical component of the dopaminergic reward system. In addition, it is of key importance for the motivation and emotional regulation of maternal behavior:141. The ventral tegmentum, ventromedial prefrontal cortex, and amygdala, also part of the dopaminergic regions of the brain, also play a very important role in the reward system:143-144.

Other subsystems

Hormone

Increased dopamine levels

An increase in the level of dopamine in the blood plasma occurs during shock, injury, burns, blood loss, stress, various pain syndromes, anxiety, and fear. Dopamine plays a role in the body’s adaptation to stressful situations, injuries, blood loss, etc.

Also, the level of dopamine in the blood increases when the blood supply to the kidneys deteriorates or when the content of sodium ions, angiotensin or aldosterone in the blood plasma is increased. Apparently, this occurs due to an increase in the synthesis of dopamine from DOPA in the kidney tissue during ischemia or under the influence of angiotensin and aldosterone. It is likely that this physiological mechanism serves to correct renal ischemia and to counteract hyperaldosteronemia and hypernatremia.

Pathologies

It is assumed that a decrease in dopamine levels in the mesocortical pathway is associated with negative symptoms of schizophrenia (flattening of affect, apathy, poverty of speech, anhedonia, withdrawal from society), as well as with cognitive disorders (deficits of attention, working memory, executive functions). The antipsychotic effect of neuroleptics, that is, their ability to reduce productive disorders - delusions, hallucinations, psychomotor agitation - is associated with inhibition of dopaminergic transmission in the mesolimbic pathway. Neuroleptics also inhibit dopaminergic transmission in the mesocortical pathway, which with long-term therapy often leads to increased negative disorders (see Neuroleptic deficiency syndrome).

Long-term blockade of dopamine receptors by antipsychotics leads to compensatory processes; In this regard, the dopamine hypothesis of schizophrenia has been criticized: it is argued that excessive activity in the dopamine system (increased concentration of dopamine, increased sensitivity of dopamine receptors or increase in their density) may be due not to the disease itself, but to long-term use of antipsychotics:89-90.

Parkinsonism is associated with decreased levels of dopamine in the nigrostriatal pathway. Observed with the destruction of the substantia nigra, pathology of D 1-like receptors. The inhibition of dopaminergic transmission in the nigrostriatal system is also associated with the development of extrapyramidal side effects when taking antipsychotics: drug-induced parkinsonism, dystonia, akathisia, tardive dyskinesia, etc. To treat Parkinson's disease, dopamine receptor agonists are often used (that is, dopamine analogues: pramipexole, bromocriptine, pergolide and etc.): today this is the largest group of antiparkinsonian drugs. Some of the antidepressants also have dopaminergic activity.

Disorders such as anhedonia, depression, dementia, pathological aggressiveness, fixation of pathological drives, persistent lactorrhea-amenorrhea syndrome, impotence, acromegaly, restless legs syndrome and periodic limb movements are also associated with a violation of the dopaminergic system.

Aging process

The process of normal aging is also associated with a decrease in dopamine levels in the subcortical formations and anterior parts of the brain. According to research, the aging process is manifested by a decrease in the volume and mass of the brain and a decrease in the number of synaptic connections; In addition to a decrease in the number of cerebral receptors, cerebral mediator insufficiency also occurs. With age, the number and density of dopamine D2 receptors in the striatum decreases, and the concentration of dopamine in the subcortical formations of the brain decreases. Clinical manifestations of these changes are impoverishment of facial expressions, some general slowness, hunched, senile posture, shortening of step length.

“Dopamine-sensitive” changes are also observed in the cognitive sphere: with age, reaction speed decreases, it becomes more difficult to assimilate and implement a new program of action, the level of attention and the amount of RAM decreases. In the absence of organic pathology, age-related cognitive changes do not lead to maladaptation in older people and allow them to maintain the usual rhythm of social activity.

See also

Notes

1. In Russian terminology, the name “dopamine” is accepted. The “dopamine” option is a direct transliteration of the term accepted in English literature dopamine and is not found in Russian dictionaries. The difference is explained by the difference in abbreviations resulting from the correspondence ph = ph: dihydroxy ph enylalanine = DOPA, dihydroxy f enylalanine = DOPA.
2. (undefined) . Archived from the original on August 22, 2011.
3. Biology of Happiness (undefined) . Archived from the original on August 22, 2011.
4. Your brain during sex (undefined) . Archived from the original on August 22, 2011.
5. Pleasure: dopamine (undefined) . Archived January 24, 2012.
6. Cocaine addicts can only get pleasure from the anticipation of this pleasure (undefined) . Archived January 24, 2012.
7. Dopamine and desire (undefined) . Archived from the original on August 22, 2011.
8. Markov A. Human evolution. Book 2. Monkeys, neurons and the soul. - Corpus, 2011. - T. 2. - 512 p. - (Dynasty). - 5000 copies. - ISBN 978-5-271-36294-1, 978-5-17-078089-1, 978-5-17-078089-1.
9. Zakharov V.V., Yakhno N.N. Cognitive disorders in old and senile age: A manual for doctors. - Moscow, 2005.
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