Effects of mafoprazine, a phenylpiperazine derivative, on the central dopaminergic system.
The effects of mafoprazine, a new phenylpiperazine derivative, on the central dopaminergic system were studied. Mafoprazine, like chlorpromazine and haloperidol, reduced the apomorphine-induced cage-climbing behavior in mice, emesis in dogs and stereotyped behavior in monkeys; methamphetamine-induced hyperlocomotion and group toxicity in mice; and agitation in rats. Mafoprazine inhibited the unilateral circling behavior induced by methamphetamine and apomorphine in rats with 6-hydroxydopamine-induced lesions in the unilateral nigrostriatal neuronal tract. The potency of mafoprazine in these experiments was almost equal to that of chlorpromazine and about one-tenth that of haloperidol. The cataleptogenic activity of mafoprazine was lower than those of chlorpromazine and haloperidol. Mafoprazine potentiated clonidine-induced hypothermia. These results suggest that mafoprazine has a relatively selective postsynaptic dopamine D2-receptor blocking action in the nucleus accumbens compared with chlorpromazine and haloperidol and suggest that mafoprazine also has alpha 2-adrenoceptor-stimulating actions.
Yamamura
M
M
Pharmacology Department, Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Nakagawa
H
H
Maeda
K
K
Kinoshita
K
K
Ishida
R
R
D000374:Aggression / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents; D001058:Apomorphine / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D002415:Cats; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D014839:Vomiting / Q000139:chemically induced
D014150:Antipsychotic Agents; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; C057002:mafoprazine; D003000:Clonidine; D001058:Apomorphine