利苏瑞ide对L - 5 -羟色氨酸诱导的大鼠头部抽搐的拮抗作用：一种5 -羟色胺混合激动剂-拮抗剂？

Antagonism of L-5-hydroxytryptophan-induced head twitching in rats by lisuride: a mixed 5-hydroxytryptamine agonist-antagonist?

作者信息

Gerber R, Barbaz B J, Martin L L, Neale R, Williams M, Liebman J M

出版信息

Neurosci Lett. 1985 Sep 30;60(2):207-13. doi: 10.1016/0304-3940(85)90245-9.

Abstract

Lisuride antagonized L-5-hydroxytryptophan (5-HTP)-induced head twitches at doses lower than those sufficient to induce the serotonin (5-HT) syndrome. Among several other 5-HT agonists tested, only LSD and 1-(m-trifluoromethylphenyl)-piperazine (TFMPP) shared this paradoxical profile. Assessment of various dopamine (DA) agonists revealed a lack of correlation between DA-mediated stereotyped behavior (indicative of postsynaptic DA agonism) and blockade of 5-HTP-induced head twitches. Lisuride displaced specific ligand binding from putative S1a, S1b and S2 receptors at nanomolar concentrations, and other drugs that blocked 5-HTP-induced head twitches also displaced binding at S2 sites. It is proposed that lisuride may have agonist properties at S1a receptors mediating the 5-HT syndrome but antagonist properties at S2 receptors mediating 5-HTP-induced head twitching.

摘要

利苏瑞ide在低于足以诱发血清素（5-HT）综合征的剂量下，拮抗L-5-羟色氨酸（5-HTP）诱导的头部抽搐。在测试的其他几种5-HT激动剂中，只有麦角酸二乙胺（LSD）和1-（间三氟甲基苯基）-哌嗪（TFMPP）具有这种矛盾的特征。对各种多巴胺（DA）激动剂的评估显示，DA介导的刻板行为（指示突触后DA激动作用）与5-HTP诱导的头部抽搐的阻断之间缺乏相关性。利苏瑞ide在纳摩尔浓度下从假定的S1a、S1b和S2受体上取代特异性配体结合，并且其他阻断5-HTP诱导的头部抽搐的药物也在S2位点取代结合。有人提出，利苏瑞ide在介导5-HT综合征的S1a受体上可能具有激动剂特性，但在介导5-HTP诱导的头部抽搐的S2受体上具有拮抗剂特性。