匹拉唑平与γ-氨基丁酸/苯二氮䓬受体复合物及甘氨酸受体的相互作用。

Interaction of pitrazepin with the GABA/benzodiazepine receptor complex and with glycine receptors.

作者信息

Braestrup C, Nielsen M

出版信息

Eur J Pharmacol. 1985 Nov 26;118(1-2):115-21. doi: 10.1016/0014-2999(85)90669-7.

Abstract

Pitrazepin (3-(piperazinyl-1)-9H-dibenz(c,f)triazolo(4,5-a)azepin) is a new GABAA receptor antagonist reported to antagonize electrophysiological effects of GABA. We have investigated in some detail the interaction of pitrazepin with the GABA/benzodiazepine receptor chloride channel complex. Pitrazepin was found to be a competitive inhibitor of the GABAA receptor which is coupled to [3H]diazepam and [35S]TBPS binding sites; the KI value obtained by Schild analyses was 80 nM. Although pitrazepin interacted weakly with BZ receptors the compound did not affect the chloride gating mechanism (labelled with [35S]TBPS or [3H]avermectin B1a). Further, pitrazepin was a non-selective GABA antagonist since glycine receptors, labelled with [3H]strychnine, were affected at low concentrations (the KI values in rat brain-stem were 71-110 nM).

摘要

匹拉唑平（3-（哌嗪-1-基）-9H-二苯并（c，f）三唑并（4，5-a）氮杂卓）是一种新型γ-氨基丁酸A型（GABAA）受体拮抗剂，据报道它可拮抗γ-氨基丁酸（GABA）的电生理效应。我们已经较为详细地研究了匹拉唑平与GABA/苯二氮䓬受体氯离子通道复合物的相互作用。发现匹拉唑平是GABAA受体的竞争性抑制剂，该受体与[3H]地西泮和[35S]叔丁基二环磷硫酰胺（TBPS）结合位点偶联；通过Schild分析得到的抑制常数（KI）值为80纳摩尔。尽管匹拉唑平与苯二氮䓬（BZ）受体的相互作用较弱，但该化合物并不影响氯离子门控机制（用[35S]TBPS或[3H]阿维菌素B1a标记）。此外，匹拉唑平是一种非选择性GABA拮抗剂，因为用[3H]士的宁标记的甘氨酸受体在低浓度下会受到影响（大鼠脑干中的KI值为71 - 110纳摩尔）。