Antiemetic specificity of dopamine antagonists.
Twelve antagonists of apomorphine-induced emesis in dogs were studied in different tests to evaluate their antiemetic specificity. Ten of these antagonists were neuroleptics: benzquinamide, clebopride, bromopride, prochlorperazine, haloperidol, chlorpromazine, thiethylperazine, metoclopramide, droperidol, and pimozide blocked conditioned responding in dogs and apomorphine-induced stereotyped behavior in rats. The use of these compounds as anti-emetics entails a risk of neurological side effects. Metopimazine and domperidone were devoid of neuroleptic activity. Metopimazine, however, showed potent alpha-adrenergic blocking activity, showed histamine H1 antagonism, and induced palpebral ptosis. Therapeutic doses of metopimazine are, therefore, likely to produce sedation and side-effects related to autonomic blockade, Domperidone showed potent antiemetic activity and, up to high doses, no other central or peripheral effects. Therefore, domperidone is the only specific antiemetic known.
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000008:administration & dosage; D001143:Arousal / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced; D013239:Stereotyped Behavior / Q000187:drug effects; D014363:Tryptamines / Q000008:administration & dosage; D014839:Vomiting / Q000139:chemically induced
D000932:Antiemetics; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D014363:Tryptamines; C030820:tryptamine; D001058:Apomorphine; D009638:Norepinephrine