Effect of isofloxythepin, a novel neuroleptic, on hippocampal stimulation-induced wet-dog shaking in the rat.
(+/-)Isofloxythepin (0.32-3.2 mg/kg, i.p.) significantly inhibited in a dose-dependent manner wet-dog shaking (WDS) induced by electrical stimulation of the rat hippocampus. In addition, both optical isomers of isofloxythepin inhibited WDS, with the (-)-isomer being almost 3 times more potent than the (+)-isomer. Other neuroleptics such as haloperidol, chlorpromazine, zotepine and sulpiride also reduced significantly the number of WDS. The inhibitory potency of haloperidol was comparable to that of (+/-)isofloxythepin, which was approximately 3 times more potent than that of chlorpromazine or zotepine. Sulpiride suppressed significantly WDS only at the high dose of 100 mg/kg. None of the drugs affected hippocampal afterdischarge. Inhibition of WDS produced by (+/-) isofloxythepin or haloperidol was antagonized by pretreatment with a dopamine receptor agonist, lisuride. The present results indicate that isofloxythepin shares with other neuroleptics an inhibitory effect on WDS; dopaminergic blocking action appears to be important in the inhibition of WDS induced by hippocampal stimulation.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yamamoto
T
T
Ueki
S
S
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003988:Dibenzothiepins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D008090:Lisuride / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology
D014150:Antipsychotic Agents; D003988:Dibenzothiepins; C022110:isofloxythepin; D013469:Sulpiride; D008090:Lisuride