Malick J B, Doren E, Barnett A
Pharmacol Biochem Behav. 1977 Mar;6(3):325-9. doi: 10.1016/0091-3057(77)90032-6.
Quipazine has been reported to be a direct serotonin receptor agonist. In this laboratory, quipazine produced head-twitch in mice similar to that produced by the serotonin precursor, 5-hydroxytryptophan (5-HTP). Three antiserotonergic drugs (methiothepin, methysergide, and cinanserin) antagonized both the 5-HTP and quipazine-induced head-twitch responses. In addition, the quipazine response was significantly potentiated by a monoamine oxidase (MAO) inhibitor, pargyline. Since it is not likely that quipazine itself is metabolized by MAO, these results suggested that quipazine might cause release of endogenous serotonin. Parachlorophenylalanine, a serotonin depletor, significantly antagonized the potentiation of quipazine by the MAO inhibitor but failed to antagonize the head-twitch produced by quipazine itself. The present studies suggest that quipazine influences serotonin receptors in the brain to produce head-twitch by two mechanisms of action: (1) by direct serotonin receptor activation, and (2) indirectly by causing a release of endogenous serotonin.
据报道,喹哌嗪是一种直接的血清素受体激动剂。在本实验室中,喹哌嗪在小鼠身上产生的头部抽搐类似于血清素前体5-羟色氨酸(5-HTP)所产生的头部抽搐。三种抗血清素药物(甲硫噻嗪、甲基麦角新碱和辛那色林)拮抗了5-HTP和喹哌嗪诱导的头部抽搐反应。此外,单胺氧化酶(MAO)抑制剂帕吉林显著增强了喹哌嗪的反应。由于喹哌嗪本身不太可能被MAO代谢,这些结果表明喹哌嗪可能会导致内源性血清素的释放。对氯苯丙氨酸是一种血清素消耗剂,它显著拮抗了MAO抑制剂对喹哌嗪的增强作用,但未能拮抗喹哌嗪本身产生的头部抽搐。目前的研究表明,喹哌嗪通过两种作用机制影响大脑中的血清素受体以产生头部抽搐:(1)通过直接激活血清素受体,以及(2)通过引起内源性血清素的释放间接起作用。