Dopamine
From Wikipedia, the free encyclopedia
For other uses, see Dopamine (disambiguation).
| Dopamine | |
|---|---|
 | |
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| Identifiers | |
| CAS number | 51-61-6  ,62-31-7 (hydrochloride) |
| PubChem | 681 |
| ChemSpider | 661 |
| UNII | VTD58H1Z2X |
| SMILES | |
| InChI | |
| InChI key | |
| Properties | |
| Molecular formula | C8H11NO2 |
| Molar mass | 153.18 g/mol |
| Density | 1.26 g/cm3 |
| Melting point | 128 °C, 401 K, 262 °F |
| Boiling point | decomposes |
| Solubility in water | 60.0 g/100 ml |
| Hazards | |
| R-phrases | R36/37/38 |
| S-phrases | S26 S36 |
 (what is this?) (verify)Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) | |
| Infobox references | |
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors—D1, D2, D3, D4, and D5—and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area.[1] Dopamine is also a neurohormonehypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary. released by the
Dopamine is available as an intravenous medication acting on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. However, because dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease and dopa-responsive dystonia, L-DOPA, which is the precursor of dopamine, can be given because it can cross the blood-brain barrier.
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[edit] History
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England.[2] It was named dopamine because it was a monoamine, and its synthetic precursor was 3,4-dihydroxyphenylalanine (L-DOPA). Dopamine's function as a neurotransmitter was first recognized in 1958 by Arvid Carlsson and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden.[3] Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not just a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline), but a neurotransmitter as well.
[edit] Biochemistry
[edit] Name and family
Dopamine has the chemical formula C6H3(OH)2-CH2-CH2-NH2. Its chemical name is "4-(2-aminoethyl)benzene-1,2-diol" and its abbreviation is "DA."As a member of the catecholamine family, dopamine is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline) in the biosynthetic pathways for these neurotransmitters.
The effects of drugs that reduce dopamine activity
In humans, drugs that reduce dopamine activity (neuroleptics, e.g. antipsychotics) have been shown to reduce motivation, cause anhedonia (inability to experience pleasure), and long-term use has been associated with the irreversible movement disorder, tardive dyskinesia.[26] Furthermore, antipsychotic drugs are associated with weight gain, diabetes, lactation, gynecomastia, drooling, dysphoria, fatigue, sexual dysfunction, and heart rhythm problems. Selective D2/D3 agonists pramipexole and ropinirole, used to treat restless legs syndrome[27] (RLS), have limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale (SHAPS).
[edit] Opioid and cannabinoid transmission
Opioid and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and food palatability (liking).[28] This could explain why animals' "liking" of food is independent of brain dopamine concentration. Other consummatory pleasures, however, may be more associated with dopamine. One study found that both anticipatory and consummatory measures of sexual behavior (male rats) were disrupted by DA receptor antagonists.[29] Libido can be increased by drugs that affect dopamine, but not by drugs that affect opioid peptides or other neurotransmitters.
[edit] Sociability
Sociability is also closely tied to dopamine neurotransmission. Low D2 receptor-binding is found in people with social anxiety. Traits common to negative schizophrenia (social withdrawal, apathy, anhedonia) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of bipolar disorder, manic subjects can become hypersocial, as well as hypersexual.[citation needed] This is credited to an increase in dopamine, because mania can be reduced by dopamine-blocking anti-psychotics.[30]
[edit] Processing of pain
Dopamine has been demonstrated to play a role in pain processing in multiple levels of the central nervous system including the spinal cord,[31] periaqueductal gray (PAG),[32] thalamus,[33] basal ganglia,[34][35] insular cortex,[36][37] and cingulate cortex.[38] Accordingly, decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson's disease.[39] Abnormalities in dopaminergic neurotransmission have also been demonstrated in painful clinical conditions, including burning mouth syndrome,[40] fibromyalgia,[41][42] and restless legs syndrome.[43] In general, the analgesic capacity of dopamine occurs as a result of dopamine D2 receptor activation; however, exceptions to this exist in the PAG, in which dopamine D1 receptor activation attenuates pain presumably via activation of neurons involved in descending inhibition.[44] In addition, D1 receptor activation in the insular cortex appears to attenuate subsequent pain-related behavior.
[edit] Salience
Dopamine may also have a role in the salience of potentially important stimuli, such as sources of reward or of danger.[45] This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned.
[edit] Behavior disorders
Deficient dopamine neurotransmission is implicated in attention-deficit hyperactivity disorder, and stimulant medications used to successfully treat the disorder increase dopamine neurotransmission, leading to decreased symptoms.[46] Consistent with this hypothesis, dopaminergic pathways have a role in inhibitory action control and the inhibition of the tendency to make unwanted actions.[47]
The long term use of levodopa in Parkinson's disease has been linked to dopamine dysregulation syndrome.[48]
[edit] Latent inhibition and creative drive
Dopamine in the mesolimbic pathway increases general arousal and goal directed behaviors and decreases latent inhibition; all three effects increase the creative drive of idea generation. This has led to a three-factor model of creativity involving the frontal lobes, the temporal lobes, and mesolimbic dopamine.[49]
[edit] Chemoreceptor trigger zone
Dopamine is one of the neurotransmitters implicated in the control of nausea and vomiting via interactions in the chemoreceptor trigger zone. Metoclopramide is a D2-receptor antagonist that functions as a prokinetic/antiemetic.
[edit] Dopaminergic mind hypothesis
The dopaminergic mind hypothesis seeks to explain the differences between modern humans and their hominid relatives by focusing on changes in dopamine.[50] It theorizes that increased levels of dopamine were part of a general physiological adaptation due to an increased consumption of meat around two million years ago in Homo habilis, and later enhanced by changes in diet and other environmental and social factors beginning approximately 80,000 years ago. Under this theory, the "high-dopamine" personality is characterized by high intelligence, a sense of personal destiny, a religious/cosmic preoccupation, an obsession with achieving goals and conquests, an emotional detachment that in many cases leads to ruthlessness, and a risk-taking mentality. High levels of dopamine are proposed to underlie increased psychological disorders in industrialized societies. According to this hypothesis, a "dopaminergic society" is an extremely goal-oriented, fast-paced, and even manic society, "given that dopamine is known to increase activity levels, speed up our internal clocks and create a preference for novel over unchanging environments."[50] In the same way that high-dopamine individuals lack empathy and exhibit a more masculine behavioral style, dopaminergic societies are "typified by more conquest, competition, and aggression than nurturance and communality."[50] Although behavioral evidence and some indirect anatomical evidence (e.g., enlargement of the dopamine-rich striatum in humans)[51] support a dopaminergic expansion in humans, there is still no direct evidence that dopamine levels are markedly higher in humans relative to other apes.[52] However, recent discoveries about the sea-side settlements of early man may provide evidence of dietary changes consistent with this hypothesis.[53]
[edit] Links to psychosis
Main article: Dopamine hypothesis of schizophrenia
Abnormally high dopaminergic transmission has been linked to psychosis and schizophrenia.[54] Increased dopaminergic functional activity, specifically in the mesolimbic pathway, is found in schizophrenic individuals. Anti-psychotic medications act largely as dopamine antagonists, inhibiting dopamine at the receptor level, and thereby blocking the effects of the neurochemical in a dose-dependant manner. The older, so-called typical antipsychotics most commonly act on D2 receptors,[55] while the atypical drugs also act on D1, D3 and D4 receptors.[56][57] The finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine levels by more than tenfold,[58] can temporarily cause psychosis, provides further evidence for this link.[5
Therapeutic use
Main article: L-DOPA
Levodopa is a dopamine precursor used in various forms to treat Parkinson's disease and dopa-responsive dystonia. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, dopa decarboxylase), such as carbidopa or benserazide. Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase are also used. These include entacapone and tolcapone.
