Pharmacologic activity of CI-977, a selective kappa opioid agonist, in rhesus monkeys.
CI-977 is a selective, nonpeptide kappa opioid agonist. In rhesus monkeys, CI-977 is a potent antinociceptive agent against thermal stimuli after i.m. administration. Increasing the intensity of the nociceptive stimulus can reduce the analgesic activity of CI-977. Antinociceptive activity also was seen when PD 126212, containing CI-977 as the (-)-enantiomer, was administered sublingually. Naloxone antagonized the antinociceptive action of CI-977, demonstrating opiate receptor involvement in this activity. Monkeys treated with CI-977 also showed sedation at doses close to those required to produce antinociception. As with morphine, the sedative properties of CI-977 were associated with impaired cognitive performance. Aged monkeys appeared more sensitive than young monkeys to the performance-impairing effect of CI-977. Tolerance developed to the antinociceptive and response-suppressing effects. CI-977 was approximately 1000 times more potent than morphine as an analgesic when tested against a moderate (50 degrees C) thermal stimulus but less effective than morphine against a strong (55 degrees C) thermal stimulus.
Davis
R E
RE
Department of Pharmacology, Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, Michigan.
Callahan
M J
MJ
Dickerson
M
M
Downs
D A
DA
D000818:Animals; D001572:Benzofurans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control*; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects
D001572:Benzofurans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine; C067110:enadoline