[Behavioral pharmacological and electroencephalographic effects of the 5-HT1A partial agonist ipsapirone].
The behavioral and EEG effects of the 5-HT1A partial agonist ipsapirone were investigated to determine its pharmacological characteristics as an anxiolytic drug in rats, mice and rabbits, as compared with those of buspirone and diazepam. 1) The anticonflict effect of ipsapirone was almost equipotent as that of buspirone and less potent than that of diazepam in rats. Ro15-1788 antagonized the anticonflict effect of diazepam, but did not that of ipsapirone. 2) Muricide in midbrain raphe-lesioned and olfactory bulbectomized rats was inhibited by ipsapirone. However, the inhibition of muricide by ipsapirone was attenuated by its repeated administration. 3) The muscle relaxant effects of ipsapirone and buspirone on rotarod performance were less potent than that of diazepam. Ethanol-induced muscle relaxation was markedly potentiated by diazepam, but less potently by ipsapirone and buspirone. 4) The pentetrazol-induced convulsion was dose-dependently antagonized by diazepam, while it was weakly potentiated by ipsapirone and buspirone. 5) The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation in rabbits were markedly inhibited by diazepam. Conversely, ipsapirone and buspirone slightly potentiated afterdischarges. In conclusion, it is suggested that ipsapirone has anxiolytic activities similar to that of buspirone and moderate antimuricidal action. In addition, ipsapirone, like buspirone, is also characterized by its less potent muscle relaxant, alcohol-potentiating and anticonvulsant actions.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
T
T
Yamamoto
S
S
Shibata
K
K
Teshima
Y
Y
Inoue
M
M
Ushio
K
K
Tominaga
M
M
Ohno
S
S
Watanabe
S
S
Ueki
D000818:Animals; D014151:Anti-Anxiety Agents; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects*; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D012701:Serotonin; D005442:Flumazenil; C043077:ipsapirone; D003975:Diazepam; D002065:Buspirone