Matsumoto K, Mizowaki M, Takayama H, Sakai S, Aimi N, Watanabe H
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.
Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):319-23. doi: 10.1016/s0091-3057(96)00314-0.
We investigated the effects of mitragynine, a major alkaloid isolated from the leaves of Mitragyna speciosa Korth (Rubiaceae), on the 5-HT2A receptor-mediated head-twitch response in mice. Intraperitoneal injection of mitragynine (5-30 mg/kg), as well as intraperitoneal injection of 5-HT2A receptor antagonist ritanserin, inhibited the 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT: 16 mg/kg, IP)-induced head-twitch response in a dose-dependent manner. In contrast, mitragynine affected neither head-weaving caused by 5-MeO-DMT, nor drug-free spontaneous motor activity. Pretreatment of mice with reserpine (5 mg/kg, IP), p-chlorophenylalanine (p-CPA, 300 mg/kg x 3 times, IP), or 6-hydroxydopamine (6-OHDA, 50 micrograms/mouse, ICV) plus nomifensine (5 mg/kg, IP) did not change the suppressant effect of mitragynine on the head-twitch response caused by 5-MeO-DMT. On the other hand, the alpha 2-adrenoceptor antagonists yohimbine (0.5 mg/kg, IP), and idazoxan (0.2 mg/kg, IP), significantly attenuated the suppressant effect of mitragynine. Lesion of central noradrenergic systems by 6-OHDA plus nomifensine did not alter the effect of idazoxan (0.2 mg/kg) on mitragynine-induced suppression of the head-twitch response. These results indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5-HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated head-twitch response by mitragynine.
我们研究了从帽柱木（茜草科）叶中分离出的主要生物碱——帽柱木碱对小鼠5-羟色胺2A（5-HT2A）受体介导的头部抽搐反应的影响。腹腔注射帽柱木碱（5 - 30毫克/千克）以及腹腔注射5-HT2A受体拮抗剂利坦色林，均以剂量依赖的方式抑制了5-甲氧基-N,N-二甲基色胺（5-MeO-DMT：16毫克/千克，腹腔注射）诱导的头部抽搐反应。相比之下，帽柱木碱既不影响由5-MeO-DMT引起的头部摆动，也不影响无药物时的自发运动活动。用利血平（5毫克/千克，腹腔注射）、对氯苯丙氨酸（p-CPA，300毫克/千克×3次，腹腔注射）或6-羟基多巴胺（6-OHDA，50微克/只小鼠，脑室内注射）加诺米芬辛（5毫克/千克，腹腔注射）对小鼠进行预处理，并没有改变帽柱木碱对5-MeO-DMT引起的头部抽搐反应的抑制作用。另一方面，α2-肾上腺素能受体拮抗剂育亨宾（0.5毫克/千克，腹腔注射）和咪唑克生（0.2毫克/千克，腹腔注射）显著减弱了帽柱木碱的抑制作用。6-OHDA加诺米芬辛对中枢去甲肾上腺素能系统的损伤并没有改变咪唑克生（0.2毫克/千克）对帽柱木碱诱导的头部抽搐反应抑制作用的影响。这些结果表明，突触后α2-肾上腺素能受体的刺激、5-HT2A受体的阻断或两者兼而有之，参与了帽柱木碱对5-HT2A受体介导的头部抽搐反应的抑制作用。
