Classification of narcotics on the basis of their reinforcing, discriminative, and antagonist effects in rhesus monkeys.

Drug discrimination and drug reinforcement procedures were used to classify a variety of narcotic agonists, mixed agonist-antagonists, and antagonists in the rhesus monkey. A five-way classification was formed. Morphine-like agonists were compounds that shared the capacities to reinforce responding, to produce discriminative stimulus effects similar to those of morphine, and to suppress withdrawal in morphine-dependent rhesus monkeys. Morphine-like mixed agonists-antagonists were differentiated from pure agonists primarily by their capacity to elicit abstinence signs in morphine-dependent monkeys. A third class of narcotic agonists had ethylketazocine as a prototype. These compounds shared a distinctive set of interoceptive stimuli, failed to maintain significant responding relative to morphine-like agonists, and neither suppressed nor elicited withdrawal in morphine-dependent rhesus monkeys. The ethylketazocine-like mixed agonist-antagonists were similar to the ethylketazocine-like agonists, except that they shared the capacity to precipitate a morphine withdrawal syndrome. Narcotic antagonists (e.g., naltrexone) did not share interoceptive effects with either morphine or ethylketazocine, but were able to block the discriminative effects of both types of agonists. Furthermore, narcotic antagonists induced narcotic abstinence in morphine-dependent rhesus monkeys. The present classification scheme may be useful in identifying the properties of new narcotics, for clarifying relationships between narcotics and other pharmacological classes, and in comparing classifications based on other effects of narcotics.