Effects of R-84760, a selective kappa-opioid receptor agonist, on nociception, locomotion and respiration in rats.
The effects of R-84760 [(3R)-3-(1-pyrrolidinylmethyl)-4-[(1S)-5,6-dichloro-l-indancarb onyl] tetrahydro-1,4-thiazine hydrochloride] on nociception, locomotion and respiration were examined in rats. R-84760 induced a potent antinociceptive effect in the formalin test. The potency was 930 and 1500 times higher than that of U-50488 and morphine, respectively, when injected subcutaneously. Intracerebroventricular and intrathecal injection, as well as subcutaneous administration of naloxone antagonized the antinociceptive effect of R-84760, suggesting the sites of action of R-84760 were at the spinal and supraspinal levels. R-84760 disturbed the rotarod performance at doses 16 times higher than those needed for antinociception. R-84760 did not affect the arterial blood Pco2, Po2 and pH at a supramaximal dose for antinociception.
Fujibayashi
K
K
Biological Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
Kubota-Watanabe
M
M
Iizuka
Y
Y
D000698:Analgesia; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001784:Blood Gas Analysis; D002245:Carbon Dioxide / Q000097:blood; D005557:Formaldehyde / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000188:drug therapy; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012119:Respiration / Q000187:drug effects*; D013843:Thiazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000700:Analgesics; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013843:Thiazines; D002245:Carbon Dioxide; C091101:R 84760; D005557:Formaldehyde; D009270:Naloxone; D010100:Oxygen