CHAPTER V - Opiate Antagonists in the Benzomorphan Series

Abstract

This chapter presents various studies on opiate antagonists in the benzomorphan series. It was earlier shown that nalorphine, in spite of its specific opiate antagonistic action, could affect relief of postoperative pain and morphine on an mg for mg basis. Unfortunately, the relief was accompanied by bizarre subjective reactions, which were very disturbing to the patient. However, the wide range of antagonistic potency suggested that among the antagonists, there might have been an effective analgesic that produced little or none of the disturbing nalorphine-like side effects. To this end, a number of the benzomorphans with specific antagonistic properties are under clinical investigation: SKF 10,047; Win 19,362; Win 20,228; Win 20,264; and Win 20,740. SKF 10,047 could be used clinically as an opiate antagonist, having potency equal to or greater than that of nalorphine. Win 20,740 is a most interesting compound. It was the most potent antagonist tried in the benzomorphan series that showed some analgesic effects in animals. It was a very potent analgesic in man at doses that produced no nalorphine-like subjective effects. The latter have occurred occasionally when the dose is increased severalfold.