Dopamine
Dopamine is "one of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (dopamine receptors) mediate its action."[1]
Dopamine regulates the secretion of prolactin from the anterior pituitary gland. Dopamine is released from specialised neurons of the arcuate nucleus of the hypothalamus into the blood vessels of the median eminence, which transport the dopamine to the pituitary gland where it inhibits prolactin secretion from lactotroph cells.
Physiology
Dopamine plasma membrane transport proteins
Dopamine plasma membrane transport proteins are "sodium chloride-dependent neurotransmitter symporters located primarily on the plasma membrane of dopaminergic neurons. They remove dopamine from the extracellular space by high affinity reuptake into presynaptic terminals and are the target of dopamine uptake inhibitors."[2]
Dopamine receptors
D1-like receptors
These receptors stimulate adenylate cyclase.[3]
- D1 receptors
- D5 receptors
D2-like receptors
These receptors inhibit adenylate cyclase.[4]
- Dopamine D2 receptors
Agonists, such as metoclopramide, are used as antiemetics.
Antagonists, such as risperidone and haloperidol, are used to treat schizophrenia.[5]
Blockade of the D2 receptors, which may be predisposed by genetic polymorphisms of the allele, may cause neuroleptic malignant syndrome.[6]
- D3 receptors
Agonists of D3, especially nonergot agonists such as pramipexole and ropinirole, may be used to treat Parkinonism and restless legs syndrome.[7]
- D4 receptors
Dopamine in disease
Attention deficit hyperactivity disorder
ADHD may result from reduced inhibitory dopamine transmission in the midbrain. This may be due to an increase in dopamine plasma membrane transport protein density which may remove dopamine from the synapse too quickly.[8][9]
Drug abuse
The rewarding effects of amphetamines and cocaine are due to dopamine activity. Cocaine increases monoamine levels by binding to serotonin (5-HT), norepinephrine (NE), and dopamine (DA) catecholamine plasma membrane transport proteins. This blockade prevents the reuptake of neurotransmitters, thus increasing the amount available at the synapse to bind to the post synaptic cell. In contrast to amphetamine, a similar psychomotor stimulant, cocaine is a dopamine uptake inhibitor and does not stimulate DA release.[10] Cocaine's rewarding effects come primarily from increased activity in the mesolimbic dopamine pathway.[11]
Novelty Seeking Personality Trait
Novelty seeing personality trait may be related to polymorphisms in the dopamine receptor D4 that affects dopamine activity in the tuberoinfundibular dopaminergic system.[12]
Parkinsonism
Schizophrenia
The dopamine hypothesis proposes that schizophrenia is in part due to excessive dopaminergic activity.[13]
Clinical pharmacology
Dopamine agonists
Dopamine agonists are "dugs that bind to and activate dopamine receptors."[14]
Agonists of dopamine receptor D3, especially nonergot agonists such as pramipexole and ropinirole, may be used to treat Parkinonism and restless legs syndrome.[7]
Dopamine antagonists
Dopamine antagonists are "drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with neuroleptic malignant syndrome."[15]
Dopamine uptake inhibitors
Dopamine uptake inhibitors are "drugs that block the transport of dopamine into axon terminals or into storage vesicles within terminals. Most of the adrenergic uptake inhibitors also inhibit dopamine uptake."[16] Dopamine uptake inhibitors affect dopamine plasma membrane transport proteins.
Examples include amphetamines, bupropion, cocaine, and methylphenidate. Some of these drugs are also adrenergic uptake inhibitors.
References
- ↑ Anonymous (2024), Dopamine (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Dopamine plasma membrane transport protein (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Receptors, Dopamine D1 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Receptors, Dopamine D2 (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Katzung, Bertram G. (2001). Basic & clinical pharmacology. New York: Lange Medical Books/McGraw-Hill, 483. ISBN 0-8385-0598-8.
- ↑ Kishida I, Kawanishi C, Furuno T, Kato D, Ishigami T, Kosaka K (2004). "Association in Japanese patients between neuroleptic malignant syndrome and functional polymorphisms of the dopamine D(2) receptor gene". Mol. Psychiatry 9 (3): 293-8. DOI:10.1038/sj.mp.4001422. PMID 15094790. Research Blogging.
- ↑ 7.0 7.1 Baker WL, White CM, Coleman CI (2008). "Effect of nonergot dopamine agonists on symptoms of restless legs syndrome". Ann Fam Med 6 (3): 253–62. DOI:10.1370/afm.845. PMID 18474889. Research Blogging.
- ↑ Volkow, Nora D.; Gene-Jack Wang, Scott H. Kollins, Tim L. Wigal, Jeffrey H. Newcorn, Frank Telang, Joanna S. Fowler, Wei Zhu, Jean Logan, Yeming Ma, Kith Pradhan, Christopher Wong, James M. Swanson (2009-09-09). "Evaluating Dopamine Reward Pathway in ADHD: Clinical Implications". JAMA 302 (10): 1084-1091. DOI:10.1001/jama.2009.1308. Retrieved on 2009-09-09. Research Blogging.
- ↑ Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ (1999 Dec 18-25). "Dopamine transporter density in patients with attention deficit hyperactivity disorder.". Lancet 354 (9196): 2132-3. DOI:10.1016/S0140-6736(99)04030-1. PMID 10609822. Research Blogging.
- ↑ Gold LH, Geyer MA, Koob GF (1989). "Neurochemical mechanisms involved in behavioral effects of amphetamines and related designer drugs". NIDA Res. Monogr. 94: 101–26. PMID 2514360. [e]
- ↑ Kuhar MJ, Ritz MC, Boja JW (1991). "The dopamine hypothesis of the reinforcing properties of cocaine". Trends Neurosci. 14 (7): 299–302. PMID 1719677.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 601696 . World Wide Web URL: http://omim.org/.
- ↑ Katzung, Bertram G. (2001). Basic & clinical pharmacology. New York: Lange Medical Books/McGraw-Hill, 479. ISBN 0-8385-0598-8.
- ↑ Anonymous (2024), Dopamine agonists (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Dopamine antagonists (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Dopamine uptake inhibitors (English). Medical Subject Headings. U.S. National Library of Medicine.