Historical introduction and review of chemistry.

A historical introduction and review of the chemistry of the agonist-antagonist analgesics is presented. This development of strong analgesics with a lowered abuse potential from nalorphine to the clinically useful agonist-antagonists pentazocine, butorphanol, nalbuphine and buprenorphine is discussed in detail. The discovery of the pure antagonist naloxone and naltrexone is described. The possible use of cyclazocine and later naltrexone in treatment of post-dependent narcotic addicts is also described. Finally, structure-activity relationships are summarized relating changes in N-alkylation to the production of narcotic antagonist activity over all of the structural types of opioids.