Narcotic Antagonists as Analgesics

Abstract

2-Dimethylallyl- 5,9-dimethyl-2'-hydroxybenzomorphan (Win 20,228) was found to be a weak antagonist of morphine and meperidine, whereas 2-allyl-5-ethyl-2'- hydroxy-9-methyl-6,7-benzomorphan (Win 19,362) and 2-allyl-2'-hydroxy-5,9- dimethyl-6,7-benzomorphan (Win 19,631) were about three times as potent as nalorphine. Preliminary clinical trials indicate that Win 19,362 is about twice as potent as morphine as an analgesic but, like nalorphine, is capable of producing severe psychic side effects. Win 20,228 is estimated to be about half as active as morphine as an analgesic, but no bizarre psychic effects were reported at any dose tested. Studies of addiction liability with Win 20,228 in monkeys suggest that this compound will not support morphine addiction.