Pharmacological analysis of the discriminative stimulus characteristics of ethylketazocine in the rhesus monkey

Rhesus monkeys were trained to discriminate between the intramuscular injection of 10 μg/kg of ethylketazocine (EKC) and saline. Twenty consecutive responses upon the right or left lever were reinforced with food, contingent upon whether EKC or saline was administered before the session. The discriminative stimulus effect of EKC was stereospecific since the d-isomer of EKC did not produce EKC-appropriate responding over a wide range of doses, including doses 1000-fold greater than required for racemic EKC. In addition, racemic UM 1072 (an N-tetrahydrofurfuryl substituted benzomorphan) produced the EKC-discriminative effect, whereas its all-S enantiomer, UM 1071-S, at 1000-fold higher doses did not. In two monkeys, the EKC-discriminative stimulus was reversed by naltrexone, whereas in two others it was not. The EKC-discriminative stimulus appears to be centrally mediated since nalorphine produced the stimulus but a quaternary derivative of nalorphine did not. Furthermore, a quaternary derivative of naltrexone failed to reverse the discriminative effects of EKC. Other drugs that produced discriminative effects similar to those of EKC were the narcotic agonists, ketazocine and UM 909 (an N-methylfuryl substituted benzomorphan), and the mixed agonist-antagonists, cyclazocine, cyclorphan, SKF-10,047 (N-allylnormetazocine) and nalorphine. Ketamine and phencyclidine produced EKC-appropriate responses in two of four monkeys. In contrast, morphine, codeine, pentazocine, etorphine, levorphanol and meperidine, as well as the non-narcotics pentobarbital, dextrorphan and apomorphine produced primarily saline-appropriate responding over a wide range of doses, including those that markedly reduced the rate of responding. Thus, the EKC-discriminative stimulus in the rhesus monkey identifies a pharmacological class of narcotics that differ from morphine.