Importance of dopamine metabolism for clinical effects and side effects of neuroleptics.
The authors studied the relation between human central dopamine (DA) metabolism and the clinical effects of neuroleptics. The neuroleptic-induced increase in central DA turnover (an indicator for the degree of DA receptor blocking) was found to be positively correlated with the therapeutic effect of neuroleptics and the development of hypokinetic-rigid symptoms. This supplies a direct argument in support of the contention that DA antagonism is related to the occurrence of clinical effects. The authors also found indications that neuroleptics of different chemical types do not significantly differ in their intrinsic ability to provoke hypokinetic-rigid symptoms, that development of these symptoms depends on the patient's individual susceptibility, and that individual susceptibility is based on relatively low DA turnover.
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000188:drug therapy; D002746:Chlorpromazine / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007206:Individuality; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy*; D008875:Middle Aged; D010546:Perphenazine / Q000627:therapeutic use; D010919:Placebos; D014149:Tranquilizing Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D018492:Dopamine Antagonists; D010919:Placebos; D014149:Tranquilizing Agents; D006897:Hydroxyindoleacetic Acid; D010546:Perphenazine; D006220:Haloperidol; D002746:Chlorpromazine; D004298:Dopamine; D006719:Homovanillic Acid