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Quantitative studies on the antagonism by naloxone of some narcotic and narcotic‐antagonist analgesics

1 Naloxone was used to study the antagonism of the analgesic effects of some narcotics (morphine sulphate, levorphanol tartrate, and methadone hydrochloride) and narcotic antagonists (pentazocine, cyclazocine, and nalorphine hydrochloride). The analgesic assay used was the mouse phenylbenzoquinone stretching test. 2 The in vivo equivalent of a pA2 value (apparent pA2) for naloxone was determined with each agonist. These values were found to be significantly larger with the narcotics than with the narcotic antagonists. 3 The slopes in the apparent pA2 plots were also found to be significantly different. It was concluded that this difference in slopes was probably not due to a lack of equilibrium in one of the two groups of analgesics. 4 The results suggest that the narcotic and the narcotic‐antagonist analgesics may inhibit stretching in this assay by interacting either with two different receptors or with the same receptor in a different manner.