Atkinson E R, Battista S P, Ary I E, Richardson D G, Harris L S, Dewey W L
J Pharm Sci. 1976 Nov;65(11):1682-5. doi: 10.1002/jps.2600651129.
Derivatives of apomorphine and of N-n-propylnorapomorphine were prepared to obtain modified pharmacological activity and enhanced chemical stability. Mouse profile and dog emesis screens were performed, and the activity of various N-substituted derivatives and their esters was evaluated and compared to the parent compounds. The N-n-propyl diacetate derivative and N-methyl and N-n-propyl ascorbate salts were remarkably stable to air: apomorphine etherate was no more stable than the free base. The dimers, the major products formed during the acid-catalyzed rearrangement of morphines to apomorphines, were all potent emetics. Additionally, two showed a significant antagonism to morphine in mice and dogs.
制备了阿扑吗啡和N-正丙基去甲阿扑吗啡的衍生物，以获得改良的药理活性和增强的化学稳定性。进行了小鼠实验和犬催吐筛选，并评估了各种N-取代衍生物及其酯的活性，并与母体化合物进行了比较。N-正丙基二乙酸酯衍生物以及N-甲基和N-正丙基抗坏血酸盐对空气非常稳定：阿扑吗啡醚化物的稳定性并不比游离碱更高。二聚体是吗啡在酸催化重排为阿扑吗啡过程中形成的主要产物，均具有强效催吐作用。此外，其中两种在小鼠和犬体内对吗啡表现出显著的拮抗作用。
