潜在抗抑郁药物非那佐辛的外周药理学研究。

Studies on the peripheral pharmacology of fenazoxine, a potential antidepressant drug.

Bassett J R, Cairncross K D, Hacket N B, Story M

Br J Pharmacol. 1969 Sep;37(1):69-78. doi: 10.1111/j.1476-5381.1969.tb09523.x.

Abstract

The action of fenazoxine, a cyclized analogue of orphenadrine, has been studied on peripheral tissues innervated by adrenergic and cholinergic nerves. The hypothesis that cyclization of the alkyl amino chain of orphenadrine results in a molecule which retains the noradrenaline sensitizing action of orphenadrine but lacks the antimuscarinic activity has been investigated.2. The antimuscarinic activity of fenazoxine, on guinea pig ileum, was approximately 1/30 that of orphenadrine.3. Fenazoxine, desmethylimipramine and cocaine potentiated the response to noradrenaline and sympathetic nerve stimulation on the cat nictitating membrane, isolated rabbit ear artery and isolated driven atrial strip preparations.4. On the driven atrial strip preparation, fenazoxine at concentrations of 5 x 10(-7)M and 1 x 10(-6)M produced a small potentiation of the inotropic response to isoprenaline. At 5 x 10(-6)M and 5 x 10(-5)M fenazoxine antagonized the inotropic response to tyramine.5. Chronic denervation of the cat nictitating membrane abolished the potentiating action of fenazoxine.6. The results presented suggest that fenazoxine inhibits the uptake of catecholamines in a manner similar to that reported for desmethylimipramine and cocaine.7. Evidence is also presented which suggests that fenazoxine, like desmethylimipramine, possesses anti-noradrenaline activity at higher concentrations.

摘要

已对苯那唑嗪（一种奥芬那君的环化类似物）对由肾上腺素能神经和胆碱能神经支配的外周组织的作用进行了研究。已对以下假说进行了研究：奥芬那君烷基氨基链的环化产生一种分子，该分子保留了奥芬那君的去甲肾上腺素致敏作用，但缺乏抗毒蕈碱活性。
苯那唑嗪对豚鼠回肠的抗毒蕈碱活性约为奥芬那君的1/30。
苯那唑嗪、去甲丙咪嗪和可卡因增强了猫瞬膜、离体兔耳动脉和离体驱动心房肌条制备物对去甲肾上腺素和交感神经刺激的反应。
在驱动心房肌条制备物上，浓度为5×10⁻⁷M和1×10⁻⁶M的苯那唑嗪对异丙肾上腺素的变力反应产生了轻微增强作用。在5×10⁻⁶M和5×10⁻⁵M时，苯那唑嗪拮抗了对酪胺的变力反应。
猫瞬膜的慢性去神经支配消除了苯那唑嗪的增强作用。
所呈现的结果表明，苯那唑嗪以类似于去甲丙咪嗪和可卡因报道的方式抑制儿茶酚胺的摄取。
还提供了证据表明，苯那唑嗪与去甲丙咪嗪一样，在较高浓度时具有抗去甲肾上腺素活性。