Interactions between narcotic agonists, partial agonists and antagonists evaluated by schedule-controlled behavior.

The effects of morphine, butorphanol, cyclazocine, ketocyclazocine, ethylketocyclazocine, and SKF-10,047 were tested, alone and in conjunction with naloxone or naltrexone, in rats responding under a fixed-interval, 5-min schedule of food presentation. Except for naloxone and naltrexone, all of the drugs decreased the average rate of responding in a dose-dependent manner. The rate-decreasing effects of morphine were markedly antagonized by naltrexone, while the effects of SKF-10,047 or high doses of cyclazocine were not antagonized by naltrexone or naloxone. Naltrexone and naloxone were able to antagonize the effects of butorphanol, ketocyclazocine, ethylketocyclazocine and low doses of cyclazocine, but these drugs were considerably more difficult to antagonize than was morphine. Thus, the interactions between these drugs and the narcotic antagonists allow the classification of the drugs into three groups, based on a marked shift, a moderate shift or no shift in the dose-response curve. This classification is consistent with the hypothesis of Martin et al., (Journal of Pharmacology and Experimental Therapeutics, 197: 517-532, 1976) regarding distinct receptors for morphine and related drugs (mu agonists), ketocyclazocine and ethylketocyclazocine (kappa agonists) and SKF-10,047 (sigma agonist).