Bhargava H N, Cao Y J
Department of Pharmaceutics and Pharmacodynamics (m/c 865), University of Illinois at Chicago, Health Sciences Center 60612, USA.
Brain Res. 1997 Oct 17;771(2):343-6. doi: 10.1016/s0006-8993(97)00914-1.
The effects of noribogaine, a metabolite of ibogaine, on the development of tolerance to the antinociception action of morphine was determined in male Swiss-Webster mice. Ibogaine is an alkaloid isolated from the bark of the African shrub, Tabernanthe iboga. Morphine tolerance in mice was developed by two different methods. Mice were rendered tolerant to morphine either by subcutaneous implantation of a pellet containing 25 mg morphine free base for 4 days or by injecting morphine (20 mg/kg, s.c.) twice a day for 4 days. Placebo pellet implanted mice or vehicle injected mice served as controls. To determine the effect of intraperitoneally administered noribogaine on tolerance development, the drug was injected in the appropriate dose twice a day. In pellet implanted mice, a dose of 20 mg/kg of noribogaine attenuated the tolerance to morphine whereas lower doses had no effect. Similarly, in mice given multiple injections of morphine, noribogaine attenuated tolerance development at 20 and 40 mg/kg doses. Previous studies from this laboratory had shown that ibogaine at 40 and 80 mg/kg doses inhibited tolerance to morphine. Because noribogaine could attenuate morphine tolerance at lower doses than ibogaine, it is concluded that the attenuating effect of ibogaine on morphine tolerance may be mediated by its conversion to noribogaine, a more active metabolite.
在雄性瑞士-韦伯斯特小鼠中，确定了伊博格碱的代谢产物去甲伊博格碱对吗啡抗伤害感受作用耐受性发展的影响。伊博格碱是从非洲灌木伊博格树的树皮中分离出的一种生物碱。小鼠的吗啡耐受性通过两种不同方法产生。小鼠通过皮下植入含25mg吗啡游离碱的药丸4天或每天两次注射吗啡（20mg/kg，皮下注射）4天来产生对吗啡的耐受性。植入安慰剂药丸的小鼠或注射赋形剂的小鼠作为对照。为了确定腹腔注射去甲伊博格碱对耐受性发展的影响，该药物以适当剂量每天注射两次。在植入药丸的小鼠中，20mg/kg剂量的去甲伊博格碱减弱了对吗啡的耐受性，而较低剂量则无作用。同样，在多次注射吗啡的小鼠中，20mg/kg和40mg/kg剂量的去甲伊博格碱减弱了耐受性发展。该实验室先前的研究表明，40mg/kg和80mg/kg剂量的伊博格碱抑制对吗啡的耐受性。由于去甲伊博格碱能在比伊博格碱更低的剂量下减弱吗啡耐受性，因此得出结论，伊博格碱对吗啡耐受性的减弱作用可能是由其转化为更具活性的代谢产物去甲伊博格碱介导的。
