Psychiatric disorders dopamine receptors

Dopamine activity can be enhanced in one of four main ways. Medications can stimulate dopaminergic nerve cells to release dopamine into the synapse. This is the way that stimulants such as methylphenidate (Ritalin), dextroamphetamine (Dexe-drine), and dextroamphetamine/amphetamine (Adderall) work. In addition, certain drugs of abuse, notably cocaine and methamphetamine, act in part in this way. Providing more of the raw material that nerve cells use to manufacture dopamine can also increase dopamine activity. This is the approach that neurologists use when they prescribe L-DOPA (Sinemet) to patients with Parkinson s disease. Nerve cells convert L-DOPA into dopamine. L-DOPA otherwise has little place in the treatment of psychiatric disorders. Dopamine activity can also be increased by medications that directly stimulate dopamine receptors. Bromocriptine, another medication used to... 

Pearlson, G. D., Wong, D. F., Tune, L. E. et al. In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder. Arch. Gen. Psychiatr. 52 471-177, 1995. 

Dikeos, D. G., Papadimitiiou, G. N., Avramopoulos, D., et al. (1999) Association between the dopamine receptor gene locus (DRD3) and unipolar affective disorder. Psychiatr. Genet. 9, 189-195. 

Dopamine has been implicated in a number of psychiatric conditions of which schizophrenia and the affective disorders are the most widely established. Five major subtypes of dopamine receptors have now been cloned. These are divided into two main groups, and D2 respectively. The receptors consist of Di and D5 types and are positively linked to the adenylate cyclase second messenger system, while the D2 group consists of the D2, D3 and D4 receptors which are negatively linked to the adenylate cyclase system. 

Foote SL, Freedman R, Oliver AP Effects of putative neurotransmitters on neuronal activity in monkey auditory cortex. Brain Res 86 229-242, 1975 Ford DE, Kamerow DB Epidemiologic study of sleep disturbances and psychiatric disorders an opportunity for prevention JAMA 262 1479-1484, 1985 Foreman MM, Gehlert DR, Schaus JM Quinelorane, a potent and selective dopamine agonist for the D2-like receptor family. Neurotransmissions 11 1 -5, 1995 Forn J, Valdecasas FG Effects of lithium on brain adenyl cyclase activity. Biochem Pharmacol 20 2773-2779, 1971... 

Whitworth P, Kendall DA Effects of lithium on inositol phospholipid hydrolysis and inhibition of dopamine D, receptor-mediated cyclic AMP formation by carbachol in rat brain slices. J Neurochem 53 536-541, 1989 Whybrow PC The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric disorder. Acta Med Austriaca 21 44-47, 1994 Whybrow PC Update on thyroid axis approaches to treatment of rapid cycling bipolar disorder. Paper presented at the annual meeting of the New Clinical Drug Evaluations Unit (NCDEU), Boca Raton, EL, May 30, 1996... 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

Confusion, hallucinations, delusions, and other psychiatric reactions are potential complications of dopaminergic treatment and are more common and severe with dopamine receptor agonists than with levodopa. Disorders of impulse control may lead to compulsive gambling, shopping, betting, sexual activity, and other behaviors. They clear on withdrawal of the offending medication. 

Chlorpromazine Blockade of D2 receptors >> 5 2 receptors .-Receptor blockade (fluphenazine least) muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) Hx-receptor blockade (chlorpromazine, thiothixene) t central nervous system (CNS) depression (sedation) t decreased seizure threshold t QT prolongation (thioridazine) Psychiatric schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) nonpsychiatric antiemesis, preoperative sedation (promethazine) pruritus Oral and parenteral forms, long half-lives with metabolism-dependent elimination Toxicity Extensions of effects on a - and M- receptors blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardivedyskinesia, and hyperprolactinemia... 

Zhang A, NeumeyerJL, Baldessarini RJ. Recent progress in development of dopamine receptor subtype-selective agents Potential therapeutics for neurological and psychiatric disorders. Chem Rev 2007 107 274. 

Lannfelt, Lars, Pierre Sokoloff, Marie-Pascale Martres, Catherine Pilon, Bruno Giros, Erik Jonsson, Gran Sedvall, and Jean-Charles Schwartz. 1992. "Amino Acid Substitution in the Dopamine D3 Receptor as a Useful Polymorphism for Investigating Psychiatric Disorders." Psychiatric Genetics 2 249-56. 

Antipsychotics have been used to promote sleep in resistant insomnia occurring as part of another psychiatric disorder, probably due to a combination of 5HT2-receptor, -adrenoceptor and histanaine Hj-receptor antagonism, in addition to their primary dopamine antagonist effects. Their long action leads to daytime sedation and extrap5n a-midal movement disorders may result from dopamine receptor blockade (see p. 380, Antipsychotics). Nevertheless, modern antipsychotics, e.g. quetia-pine, have been occasionally used for intractable insonmia. 

Abrams DB, Monti PM, Carey KB, Pinto RP, Jacobus SI (1988) Reactivity to smoking cues and relapse two studies of discriminant validity. Behav Res Ther 26(3) 225-233 American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn (DSM-IV). American Psychiatric Association, Washington, DC Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65(3) 1157-1165... 

D haenen HA, Bossuyt A Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biol Psychiatry 35 128-132, 1994 Di Costanzo E, Schifano E Dthium alone or in combination with carbamazepine for the treatment of rapid-cycling bipolar affective disorder. Acta Psychiatr Scand 83 456-459, 1991... 

In addition to acute and chronic schizophrenia, the neuroleptics are sometimes used in the management of mania, delirium, and severe agitation, whatever the cause of these symptom complexes. It must be noted that unlike parkinsonism, where a definite dysfunction in the DA system has been established, for schizophrenia and other psychiatric diseases, no unequivocal evidence has yet been presented to prove that there is a disturbance of the DA system (e.g., dopaminergic overactivity or receptor hypersensitivity). In untreated schizophrenics the production of DA metabolites is normal. Conflicting results have been obtained in studies of the DA receptors in schizophrenics (11,12,13), but in the case of patients who have not received neuroleptics, the receptor density and affinity appear to be normal (13). The "dopamine hypothesis" in these disorders derives from the beneficial effects of drugs that block DA receptors. 

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