Pathophysiology of antipsychotic drug-induced movement disorders.
Explaining the underlying mechanisms of antipsychotic drug-induced movement disorders remains a substantial challenge. The association of atypical antipsychotic agents with fewer drug-induced movement disorders than conventional agents has engendered several pathophysiologic hypotheses: (1) the hypothesis that, unlike conventional antipsychotic agents, atypical antipsychotics have greater activity in blocking serotonin-2A (5-HT(2A)) receptors than dopamine-2 (D(2)) receptors, which mitigates extrapyramidal symptoms; (2) the hypothesis that atypical antipsychotics block D(2) receptors only long enough to cause an antipsychotic action, but not as long as conventional agents; (3) the hypothesis that, in tardive dyskinesia, the nigrostriatal dopamine receptor system might develop increased sensitivity to dopamine as a result of treatment with conventional antipsychotic drugs, but this may not occur with atypical antipsychotics; and (4) the hypothesis that there might be a genetic association in tardive dystonia relating to the dopamine D(3) allele. A number of factors contribute to the difficult task of gaining insight into the pathophysiologic processes of antipsychotic agents and why these agents may lead to drug-induced movement disorders.
Casey
Daniel E
DE
Department of Psychiatry and Neurology, Oregon Health and Sciences University, Portland, OR 97321, USA. caseyd@ohsu.edu
D000367:Age Factors; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology*; D065127:Dopamine D2 Receptor Antagonists; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D012737:Sex Factors
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D058830:Serotonin 5-HT2 Receptor Antagonists