Kappa opioids in rhesus monkeys. I. Diuresis, sedation, analgesia and discriminative stimulus effects

The effects of the kappa agonists bremazocine, ethylketazocine, tifluadom and U-50,488 were examined in rhesus monkeys with four experimental procedures: urinary output was measured in normally hydrated monkeys; muscle relaxation and stupor were observed; and the time it took monkeys to withdraw their tails from warm water was evaluated. Lastly, the kappa agonists were examined in monkeys trained to respond differentially in the presence or absence of ethylketazocine. For comparison, morphine and another kappa agonist, Mr 2033, were examined under some of the procedures. Kappa agonists produced dose-dependent increases in urine output whereas morphine did not. Morphine, as well as each of the kappa agonists examined, produced dose-dependent increases in tail-withdrawal latencies from both 50 and 55°C water; analgesic doses of kappa agonists produced marked stupor and muscle relaxation. Kappa agonists produced ethylketazocine-appropriate responding in the drug discrimination procedure. Doses of kappa agonists that produced ethylketazocine-appropriate responding were similar to doses that increased urine output and smaller than doses that increased tail-withdrawal latencies. The opioid antagonist quadazocine (WIN 44,441) antagonized the effects of bremazocine, ethylketazocine, tifluadom and U-50,488.