PREVENTION OF WRITHING AND OTHER EFFECTS OF NARCOTICS AND NARCOTIC ANTAGONISTS IN MICE

¹ Department of Pharmacology, Sterling-Winthrop Research Institute, Rensselaer, New York

There was a rank-order correlation between the potencies of drugs in preventing phenylquinone-induced writhing in mice and their analgesic potencies in man within each of three groups: narcotics such as morphine; strong narcotic antagonists such as nalorphine; weak narcotic antagonists such as pentazocine. Antiwrithing potency ratios underestimated the analgesic potency ratios of narcotic antagonists, especially strong narcotic antagonists. Morphine was over 90 times more potent than nalorphine in preventing writhing. Rank orders for antiwrithing potencies of drugs were consistent with previous results, although there were inconsistencies in potency ratios, some of which may reflect differences in the sensitivity of writhing tests in detecting effects of narcotic antagonists. Within each group, the potencies of drugs in affecting writhing and rotarod performance were correlated. Within the narcotics, results of both tests correlated with Straub tail activity, and within the narcotic antagonists, with decreased locomotion. If all analgesics were taken as one group, the correlation between analgesic and antiwrithing potencies was less than that between analgesic potency and rotarod performance. Of drugs having analgesic activity in man, all seven narcoties and four of 13 narcotic antagonists prevented writhing at doses lower than those that produced other overt effects. Of nine drugs not usually called analgesics, none prevented writhing at doses lower than those that produced other effects. Among benzomorphans, the l-isomers were more potent than their d-isomers in affecting writhing and rotarod performance.

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