Studies of the dependence‐producing properties of GPA‐1657, profadol, and propiram in man

GPA‐1657, profadol, and propiram are proposed as analgesies of low abuse potential since none will suppress but each will precipitate abstinence in morphine‐dependent monkeys. GPA‐1657 is not an antagonist in man but a typical morphine‐like compound and is fudged to have significant abuse potential. Profadol and propiram act as antagonists in man and precipitate abstinence in subiects dependent on 240 mg. of morphine per day. As agonists, profadol and propiram resemble morphine‐like rather than nalorphine‐like drugs, since both produce morphine‐like subjective effects and physical dependence and suppress abstinence in subiects dependent on 60 mg. per day of morphine. Both were judged to have abuse potential. Propiram was judged to have somewhat less abuse potential than profadol, since it produces less euphoria and less physical dependence. The morphine antagonist properties of profadol and propiram are thought to be caused by the fact that they are morphine agonists with less intrinsic activity than morphine.