Analgesic effects of phencyclidine-like drugs in rhesus monkeys

Abstract

Analgesic and discriminative stimulus effects of phencyclidine (PCP), ketamine, dextrorphan, (+)-N-allyl-normetazocine [(+)-SKF 10,047] and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5,10-amine maleate (MK-801) were studied in rhesus monkeys. All five compounds increased in a dose-related manner the latency for monkeys to remove their tails from warm water with the order of potency being MK-801 greater than PCP greater than ketamine greater than (+)-SKF 10,047 greater than dextrorphan. Moreover, these effects were temperature-dependent with larger doses required to produce a maximum response when higher temperatures (i.e., 55 degrees C) were studied. The effects of PCP, ketamine, dextrorphan, (+)-SKF 10,047 and MK-801 were not attenuated by a dose (1.0 mg/kg) of the opioid antagonist quadazocine that antagonized the analgesic effects of the opioid mu agonist alfentanil and kappa agonist U-50,488. MK-801, PCP, (+)-SKF 10,047 and dextrorphan also substituted in a dose-related manner for the ketamine discriminative stimulus (1.78 mg/kg) and their relative potency as discriminative stimuli was the same as their relative potency in the tail withdrawal procedure. The apparent analgesic effects of PCP-like drugs occurred at doses 2- to 8-fold larger than doses required for discriminative stimulus effects and 3- to 10-fold smaller than doses required for anesthesia. These results support the notion that PCP-like drugs produce analgesic effects at subanesthetic doses. Moreover, the analgesic effects of PCP and related drugs in rhesus monkeys were not mediated by actions at the opioid receptors known to be associated with analgesia.