Derivatives of apomorphine and of other N-substituted norapomorphines.
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.
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004639:Emetics / Q000138:chemical synthesis; D007928:Lethal Dose 50; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors; D011930:Reaction Time / Q000187:drug effects; D013329:Structure-Activity Relationship
D004639:Emetics; D009020:Morphine; D001058:Apomorphine