On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain.
The effect of various antipsychotic drugs on the blockade of dopaminergic receptors in striatum and limbic forebrain was examined by establishing dose-response curves for the increase in HVA and for the antagonism of d-amphetamine-induced rotation in rats with unilateral lesions of the substantia nigra. A good quantitative correlation was found between dopaminergic blockade in the striatum as reflected by the ED100 for striatal HVA increase and the ED50 for rotational antagonism and the occurrence of extrapyramidal side effects in man. The ED100 for the increase in HVA in the limbic forebrain showed the same rank order of potency as those in the striatum: Haloperidol greater than primozide greater than chlorpromazine greater than thioridazine greater than clozapine. The results thus demonstrate a very good correlation between the degree of dopaminergic blockade and the increase of extrapyramidal side effects in man, but suggest the possibility of a dissociation between dopaminergic blockade and antipsychotic activity.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism*; D006801:Humans; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010648:Phenylacetates / Q000378:metabolism*; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000502:physiology; D013881:Thioridazine / Q000494:pharmacology
D014150:Antipsychotic Agents; D010648:Phenylacetates; D011955:Receptors, Drug; D010868:Pimozide; D003024:Clozapine; D006220:Haloperidol; D013881:Thioridazine; D003913:Dextroamphetamine; D002746:Chlorpromazine; D004298:Dopamine; D006719:Homovanillic Acid