PHARMACOLOGY OF N-SUBSTITUTED AZIDOMORPHINES

  • 1 January 1977
    • journal article
    • research article
    • Vol. 228  (2) , 268-292
Abstract
N-allylnorazidomorphine (NAM), N-allyl-14-hydroxynorazidomorphine (NOAM), N-cyclopropylmethylnorazidomorphine (CAM) and N-cyclopropylmethyl-14-hydroxynorazidomorphine (COAM) were synthetized and their pharmacological effect compared to naloxone and naltrexone. While naloxone and naltrexone were pure antagonists at all points, the N-substituted norazidomorphines were more potent antagonists than naloxone in some tests and extremely potent pure agonists in others. Using CAM for routine work, opiate A-receptors stimulated by CAM and opiate B-receptors antagonized by CAM were differentiated. Opiate A-receptors were involved in the behavioral disturbances (inhibition of conditioned avoidance responses, characteristic EEG changes, elimination of slow wave and paradoxical sleep) caused by the opiates. The guinea-pig ileum and mouse vas deferens were the suitable isolated organs for testing A-receptors. Opiate B-receptors were responsible for the analgesic, antitussive, cataleptic, respiratory depressant and hypotensive effects of the opiates. The isolated nictitating membrane of the cat was an appropriate model for testing the B-receptors. A-receptors may relate to cholinergic and B-receptors to adrenergic mechanisms; the N-substituted norazidomorphines are tools for the analysis of the 2 kinds of opiate receptors.