Evidence against the participation of mu- and kappa-opioid receptors in the analgesic activity of ketorolac in rats.
The possibility that activation of opioid receptors is involved in the analgesic activity of ketorolac was explored. The analgesic effects of ketorolac, of ketocyclazocine, the prototype kappa-agonist, and of morphine, the prototype mu-agonist, were assayed in the pain-induced functional impairment model in the rat. All three drugs induced a significant analgesic effect in this model. Naloxone was able to antagonize the effects of ketocyclazocine and morphine. However, the effect of ketorolac was not blocked by naloxone, although a high dose, 3.2 mg kg-1, capable of blocking kappa-receptors was used. It is concluded that activation of mu- or kappa-opioid receptors, by either a direct or an indirect mechanism, does not play a role in the analgesic activity of ketorolac.
Granados-Soto
V
V
Departamento de Farmacología y Toxicología del Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México.
Flores-Murrieta
F J
FJ
Castañeda-Hernández
G
G
Hong
E
E
López-Muñoz
F J
FJ
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D016314:Ethylketocyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D020910:Ketorolac; D009020:Morphine / Q000494:pharmacology; D009069:Movement Disorders / Q000188:drug therapy; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013997:Time Factors; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D016314:Ethylketocyclazocine; C012395:ketazocine; D009020:Morphine; D014046:Tolmetin; D020910:Ketorolac