Azidomorphines and homopyrimidazols: a new approach to the ideal analgetic.
Azidomorphines, new semi-synthetic isomorphine alkaloids and homopyrimidazols (1, 5-diazanaphtalenes), two new families of compounds favourably enlarging the scope of analgetics, were developed. Azidomorphine, a 40--50 times more potent analgetic in man than morphine, showed a remarkably great dissociation between analgetic potency and dependence capacity and proved to exert significantly less unfavourable effects than either morphine or pentazocine. Probon (Rymazolium), the first compound of the homopyrimidazol series, introduced to therapy as a new minor analgetic, potentiated the analgetic and antagonized the respiratory depressant effect of morphine and its derivatives. In patients with chronic intractable pain, a combination of azidomorphine (0.5 mg) and Probon (150 mg) achieved total pain relief without noticeable euphoria and none of the patients subjected to nalorphine-precipitation showed signs of abstinence according to the Himmelsbach scoring system. Since both the azidomorphines and the homopyrimidazols are unexploited new families, further progress in detail structure-activity relationship studies seems quite promising.
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D000882:Haplorhini; D006801:Humans; D004091:Hydromorphone / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009022:Morphine Derivatives / Q000494:pharmacology*; D010111:Oxymorphone / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D012119:Respiration / Q000187:drug effects; D019966:Substance-Related Disorders
D000700:Analgesics; D009022:Morphine Derivatives; D011743:Pyrimidines; D011744:Pyrimidinones; D009020:Morphine; D010111:Oxymorphone; D004091:Hydromorphone