Taraschenko Olga D, Panchal Vishal, Maisonneuve Isabelle M, Glick Stanley D
Center for Neuropharmacology and Neuroscience MC-136, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
Eur J Pharmacol. 2005 Apr 25;513(3):207-18. doi: 10.1016/j.ejphar.2005.03.005. Epub 2005 Apr 14.
18-Methoxycoronaridine, a synthetic iboga alkaloid congener, has been previously shown to attenuate several signs of morphine withdrawal in rats. The recently discovered action of 18-methoxycoronaridine to block alpha3beta4 nicotinic receptors may be responsible for this effect. To test this hypothesis the effects of non-selective alpha3beta4 receptor antagonists, dextromethorphan, mecamylamine, bupropion, and their combinations, were assessed on of acute naltrexone-precipitated (1 mg/kg i.p.) morphine withdrawal in rats. Dextromethorphan (5-40 mg/kg, s.c.), mecamylamine (0.25-4 mg/kg, i.p.) and bupropion (10-30 mg/kg, i.p.) alone produced variable effects on signs of withdrawal. However, two low-dose combinations, i.e., dextromethorphan (5 mg/kg, s.c.) and mecamylamine (0.25 mg/kg, i.p.), mecamylamine (0.25 mg/kg, i.p.) and bupropion (10 mg/kg, i.p.) as well as the three-drug combination significantly attenuated diarrhea and weight loss; none of the agents administered alone had these effects. The results of the present study provide evidence that alpha3beta4 nicotinic receptors are involved in the expression of at least two signs of opioid withdrawal.
18-甲氧基冠狗牙花定碱是一种合成的伊博格生物碱类似物，此前已被证明可减轻大鼠吗啡戒断的几种症状。最近发现18-甲氧基冠狗牙花定碱阻断α3β4烟碱型受体的作用可能是造成这种效应的原因。为了验证这一假设，评估了非选择性α3β4受体拮抗剂右美沙芬、美加明、安非他酮及其组合对大鼠急性纳曲酮诱发（腹腔注射1mg/kg）吗啡戒断的影响。单独使用右美沙芬（5-40mg/kg，皮下注射）、美加明（0.25-4mg/kg，腹腔注射）和安非他酮（10-30mg/kg，腹腔注射）对戒断症状产生了不同的影响。然而，两种低剂量组合，即右美沙芬（5mg/kg，皮下注射）和美加明（0.25mg/kg，腹腔注射）、美加明（0.25mg/kg，腹腔注射）和安非他酮（10mg/kg，腹腔注射）以及三种药物的组合显著减轻了腹泻和体重减轻；单独使用这些药物均无这些效果。本研究结果提供了证据，表明α3β4烟碱型受体参与了阿片类药物戒断至少两种症状的表现。
