QUINTON R M
Br J Pharmacol Chemother. 1963 Aug;21(1):51-66. doi: 10.1111/j.1476-5381.1963.tb01501.x.
In mice, yohimbine appears to accentuate the normal "alarm" reactions (alerting, flight) to external stimuli. Imipramine increases this effect and at the same time converts a non-lethal dose of yohimbine into a lethal one. The effect of imipramine is greatly reduced by adrenalectomy or by treatment with reserpine, syrosingopine, ganglion-blocking drugs or adrenaline antagonists acting on sympathetic beta-receptors. Hypnotic, anti-convulsant or anaesthetic agents, tetrabenazine or antagonists of 5-hydroxytryptamine do not reduce the imipramine effect. A variety of drugs which, like imipramine, are known to interfere with the tissue binding of noradrenaline also increase the toxicity of yohimbine. Yohimbine significantly reduces brain noradrenaline content; adrenal catechol amines are slightly reduced. The results suggest that yohimbine releases noradrenaline from stores or nerves as a consequence of increased central sympathetic activity. Imipramine increases the actions and toxicity of yohimbine by increasing the effects of the released noradrenaline on beta-receptors. The lethal effects of a high dose of yohimbine alone are not reduced by any of the treatments tested, and appear not to result from activation of sympathetic mechanisms.
在小鼠中，育亨宾似乎会增强对外部刺激的正常“警戒”反应（警觉、逃跑）。丙咪嗪会增强这种效应，同时将非致死剂量的育亨宾转变为致死剂量。肾上腺切除术或用利血平、丁苯那嗪、神经节阻断药物或作用于交感β受体的肾上腺素拮抗剂进行治疗，会大大降低丙咪嗪的效应。催眠药、抗惊厥药或麻醉剂、丁苯那嗪或5-羟色胺拮抗剂不会降低丙咪嗪的效应。已知与丙咪嗪一样会干扰去甲肾上腺素组织结合的多种药物，也会增加育亨宾的毒性。育亨宾会显著降低脑内去甲肾上腺素含量；肾上腺儿茶酚胺略有减少。结果表明，由于中枢交感神经活动增加，育亨宾会从储存部位或神经中释放出去甲肾上腺素。丙咪嗪通过增强释放的去甲肾上腺素对β受体的作用，增加育亨宾的作用和毒性。单独使用高剂量育亨宾的致死效应不会因所测试的任何治疗而降低，似乎并非由交感神经机制的激活所致。
