Hill R C, Roemer D, Buescher H
J Pharmacol Exp Ther. 1977 Jun;201(3):580-6.
In equianalgesic doses, azidomorphine is reported by J. Knoll, S. Fürst and K. Kelemen (The pharmacology of azidomorphine and azidocodeine. J. Pharm. Pharmacol. 25: 929-939, 1973) to be less likely than morphine to cause physical dependence. As the separation of the analgesic from the dependence-producing properties would represent an important contribution to the development of potent analgesic drugs, we have compared the effects of azidomorphine and morphine in a number of experiments in laboratory animals. In analgesic studies, azidomorphine was more potent than morphine in all tests and by every route of administration. However, the differences between the analgesic effects of azidomorphine and morphine were much smaller after oral than after parenteral administration. In the rhesus monkey, the programmed administration of azidomorphine over a period of 9 weeks produced physical dependence. In addition, azidomorphine was self-administered by the rhesus monkey over 3 weeks producing marked opiate-like physical dependence. It is concluded that the introduction of the azido group into the morphine molecule leads to a marked increase in analgesic activity compared with the parent drug but which does not decrease the ability to produce physical dependence.
J. 诺尔、S. 菲斯特和K. 凯莱门（《叠氮吗啡和叠氮可待因的药理学》，《药学与药理学杂志》25: 929 - 939, 1973年）报告称，在等效镇痛剂量下，叠氮吗啡比吗啡引起身体依赖性的可能性更小。由于将镇痛特性与产生依赖性的特性分离将对强效镇痛药的开发做出重要贡献，我们在多项实验中比较了叠氮吗啡和吗啡对实验动物的影响。在镇痛研究中，叠氮吗啡在所有测试中以及通过每种给药途径都比吗啡更有效。然而，口服给药后叠氮吗啡和吗啡的镇痛效果差异比非肠道给药后小得多。在恒河猴中，连续9周程序化给药叠氮吗啡会产生身体依赖性。此外，恒河猴在3周内自行服用叠氮吗啡，产生了明显的类阿片身体依赖性。得出的结论是，与母体药物相比，将叠氮基引入吗啡分子会导致镇痛活性显著增加，但不会降低产生身体依赖性的能力。
