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使用实验模型研究米安色林对单胺能系统上行和下行功能的影响(作者译)

[Effects of mianserin on functions of ascending and descending monoaminergic systems, using experimental models (author's transl)].

作者信息

Sakai Y, Deguchi T

出版信息

Nihon Yakurigaku Zasshi. 1980 Apr;76(3):213-25.

PMID:6967847
Abstract

Studies were carried out to evaluate the antidepressant action of Mianserin as related to noradrenergic and serotonergic systems. The actions of known tricyclic anti-depressants were comparatively investigated together with Mianserin (Organon). Self-stimulation behavior induced by stimulation of the posterior hypothalamus and substantia nigra was unaffected by Mianserin and imipramine, was suppressed with chlorpromazine and markedly enhanced by methamphetamine. The enhancement due to methamphetamine was suppressed by both Mianserin and chlorpromazine, and was potentiated by imipramine. Mianserin, imipramine and amitriptyline enhanced the rolling movements induced by methamphetamine in rats in which the nigro-striatal dopaminergic system was destroyed by the injection of 6-hydroxydopamine. The excitation induced by ldopa administration, of isocarboxazid treated mouse was enhanced by Mianserin in doses over 25 mg/kg and by imipramine or amitriptyline. The excitation of MK-486 treated mouse, induced by L-5HTP was suppressed by Mianserin, nortriptyline augmented the excitation. The head twitches induced by 5HTP were reduced to 1/10 in onset frequency by Mianserin, 1 mg/kg, p.o. The suppressive potency of amitriptyline in this model was less than 1/5 of that of Mianserin. The potentiation of the flexor reflex of hind limbs of the spinal rat induced by the pretreatment with isocarboxazid and l-dopa, 20 hours after the reserpinization, was markedly suppressed by Mianserin and amitriptyline, but unaffected by imipramine nor chlorimipramine. The potentiation of the extensor reflex of hind limbs of the spinal rat, induced 20 hours after the reserpinization by pretreatment with isocarboxazid and 5-HTP was suppressed by Mianserin, even in a low dose of 0.5 mg/kg, and by amitriptyline in a dose of 10 mg/kg. As far as monoaminergic mechanisms are concerned, the mode of antidepresant action of Mianserin is probably different from that of tricyclic antidepressants.

摘要

开展了多项研究以评估米安色林与去甲肾上腺素能和5-羟色胺能系统相关的抗抑郁作用。将米安色林(奥加农公司生产)与已知的三环类抗抑郁药的作用进行了对比研究。刺激下丘脑后部和黑质所诱导的自我刺激行为不受米安色林和丙咪嗪的影响,受氯丙嗪抑制,而被甲基苯丙胺显著增强。甲基苯丙胺所致的增强作用被米安色林和氯丙嗪两者抑制,而被丙咪嗪增强。米安色林、丙咪嗪和阿米替林增强了甲基苯丙胺在大鼠中诱导的翻滚运动,这些大鼠的黑质纹状体多巴胺能系统已通过注射6-羟基多巴胺而被破坏。米安色林剂量超过25mg/kg时以及丙咪嗪或阿米替林增强了异卡波肼处理的小鼠给予左旋多巴后所诱导的兴奋。米安色林抑制了L-5-羟色氨酸处理的小鼠给予5-羟色氨酸后所诱导的兴奋,去甲替林增强了该兴奋。米安色林口服1mg/kg可使5-羟色氨酸所诱导的头部抽搐发作频率降低至1/10。在该模型中,阿米替林的抑制效力不到米安色林的1/5。利血平化20小时后,异卡波肼和左旋多巴预处理所诱导的脊髓大鼠后肢屈肌反射增强被米安色林和阿米替林显著抑制,但不受丙咪嗪和氯米帕明影响。利血平化20小时后,异卡波肼和5-羟色氨酸预处理所诱导的脊髓大鼠后肢伸肌反射增强被米安色林抑制,即使是低至0.5mg/kg的剂量,以及被10mg/kg剂量的阿米替林抑制。就单胺能机制而言,米安色林的抗抑郁作用方式可能与三环类抗抑郁药不同。

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