TY - JOUR T1 - STUDIES OF ANALGESIC DRUGS. VII. MORPHINE ANTAGONISTS AS ANALGESICS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 106 LP - 116 VL - 133 IS - 1 AU - Jane Telford AU - C. N. Papadopoulos AU - Arthur S. Keats Y1 - 1961/07/01 UR - http://jpet.aspetjournals.org/content/133/1/106.abstract N2 - The purpose of this study was to survey in man some compounds possessing antimorphine activity in an attempt to identify a morphine antagonist with the analgesic potency of nalorphine but without the severe subjective side effects of nalorphine. Presumably such a compound would also be nonaddicting. To this end one dihydrocodeinone derivative, three morphinan derivatives and two derivatives of normorphine were studied for analgesic potency, respiratory depressant activity, subjective effects and ability to antagonize morphine-induced respiratory depression. One compound, (-)-3-hydroxy-N-(3,3-dimethylallyl) morphinan, possessed no morphine antagonistic activity, but did possess analgesic activity comparable to morphine and was antagonized by nalorphine. Although its side action liability was qualitatively similar to morphine, it was only half as depressant to the respiration and seemed to produce less sedation than morphine. Among the other 5 compounds, all of which were effective morphine antagonists, only (-)-3-hydroxy-N-propargyl morphinan was as potent an analgesic as nalorphine. Its side action liability was similar to that of nalorphine, with perhaps less severe but qualitatively similar subjective effects. N-allylnordihydrocodeinone was an analgesic of low potency. The analgesia which followed the other compounds was equivocal. N-methallylnormorphine in doses which produced effective morphine antagonism was essentially without side actions. In view of the seemingly obligatory side action liability of morphine-like analgesics, a comparison was made of the side action liability associated with morphine antagonism. A much wider degree of dissociation between primary and side actions was observed among the morphine antagonists than previously observed among the morphine-like drugs. The implications of this observation were discussed. ER -