The chemical and pharmacological importance of morphine analogues

The object of this review is to summarize the efforts which resulted in the discovery of therapeutically useful morphine-like drugs. The search for new analgesics can be divided into three stages: (a) search for analgesics with high efficacy and reduced unwanted side-effects; (b) understanding of structure-activity relationships; (c) studies on the mechanism of pain perception and its alleviation by investigation of the pharmacology of opioids. An immense body of literature has been produced on the syntheses of thousands of new compounds which resulted in the development of detailed structure-activity relationships. The physical and psychologic dependence of opioid analgesics also facilitated investigators to solve the problem of the separation of strong analgesia from addiction liability. In the past decades more mixed agonist-antagonist analgesics, pure antagonists devoid of agonist action and potent opioids like the 6,14-ethenomorphinan derivatives were developed. Naloxone, Naltrexone, Buprenorphine and Pentazocine are the outstanding representatives which are introduced into clinical therapy.