Moser P C, Redfern P H
School of Pharmacy and Pharmacology, University of Bath, U.K.
Eur J Pharmacol. 1988 Jul 7;151(2):223-31. doi: 10.1016/0014-2999(88)90802-3.
The effects of four benzodiazepines (diazepam, clonazepam, oxazepam and clobazam) were studied on the head-twitch response induced in mice by several 5-HT receptor agonists. All the benzodiazepines tested potentiated the effects of the directly acting agonists 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine and mescaline, without themselves inducing head-twitches. In contrast, none of them potentiated head-twitches induced by the indirectly acting agonist 5-hydroxytryptophan (5-HTP; with carbidopa 25 mg/kg), and in some experiments a clear inhibition was seen. The clonazepam (10 mg/kg) potentiation of 5-MeODMT-induced head-twitches was not antagonised by flumazenil, (+)-bicuculline, or by pretreatment with p-chlorophenylalanine. Neither was it mimicked by muscimol, which inhibited head-twitches. These results indicate that the observed potentiation is not mediated by benzodiazepine receptors and that it occurs postsynaptically to the initiating 5-HT receptors. The inability of the benzodiapines to potentiate 5-HTP-induced head-twitches probably reflects a reduction in 5-HT neuronal activity mediated by benzodiazepine receptors, as co-administration of flumazenil and clonazepam potentiated the effects of 5-HTP whereas each compound alone had no effect.
研究了四种苯二氮䓬类药物（地西泮、氯硝西泮、奥沙西泮和氯巴占）对几种5-羟色胺（5-HT）受体激动剂诱发小鼠头部抽搐反应的影响。所有受试苯二氮䓬类药物均增强了直接作用激动剂5-甲氧基-N,N-二甲基色胺（5-MeODMT）、喹哌嗪和麦司卡林的作用，而自身不诱发头部抽搐。相反，它们均未增强间接作用激动剂5-羟色氨酸（5-HTP；与25mg/kg卡比多巴合用）诱发的头部抽搐，且在某些实验中观察到明显的抑制作用。氯硝西泮（10mg/kg）对5-MeODMT诱发的头部抽搐的增强作用不受氟马西尼、（+）-荷包牡丹碱或对氯苯丙氨酸预处理的拮抗。它也未被抑制头部抽搐的蝇蕈醇模拟。这些结果表明，观察到的增强作用不是由苯二氮䓬受体介导的，而是发生在起始5-HT受体的突触后。苯二氮䓬类药物不能增强5-HTP诱发的头部抽搐可能反映了由苯二氮䓬受体介导的5-HT神经元活性降低，因为氟马西尼和氯硝西泮合用增强了5-HTP的作用，而每种化合物单独使用均无作用。
