[Pharmacological studies of d1-2-[3-(2'-chlorophenoxy)phenyl]propionic acid. (2) Sites and mechanisms of analgesic and antipyretic effects].
Effects of d1-2-[3-(2'-chlorophenoxy)phenyl]propionic acid (CPP) on the nociceptive response induced by injection of bradykinin (BK) into rabbit femoral artery were studied. When drugs were administered intravenously, the analgesic activity of morphine was 2 to 10 times more potent than that of CPP; but when it was injected into the femoral artery, CPP was approximately 5 times more potent than morphine. Intraventricular injection of a small dose of 10 micrograms/head morphine produced a prominent analgesic activity, while even a large dose of 500 micrograms/head CPP had little effect. Prostaglandin E1 (PGE1) alone in a dose range of 0.1 to 1 microgram i.a. produced no nociceptive response, but an intra-arterial pre-injection of PGE1 enhanced BK-induced nociceptive response. Morphine suppressed the BK-response pretreated with PGE1, but CPP as well as indomethacin had little effect. These results suggest that CPP suppresses BK-induced nociceptive response at the periphery, probably at the paravascular "pain receptor", and the analgesic effect of CPP may be due to inhibition of endogenous PG synthesis. On the other hand, CPP in a dose range of 2.5 to 20 mg/kg, i.v. produced antipyretic effects on the fever induced by typhoid vaccine. Intraventricular injection of 500 micrograms/head CPP produced a slight antipyretic effect. CPP had no effect on PGE1 -induced fever. These results suggest that CPP produces the antipyretic effect acting on the central nervous system, probably due to inhibition of endogenous PG synthesis.
D000527:Alprostadil; D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001920:Bradykinin / Q000494:pharmacology; D004357:Drug Synergism; D007213:Indomethacin / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010666:Phenylpropionates / Q000008:administration & dosage / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology; D011817:Rabbits
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; D011458:Prostaglandins E; C039179:2-(3-(2'-chlorophenoxy)phenyl)propionic acid; D009020:Morphine; D000527:Alprostadil; D001920:Bradykinin; D007213:Indomethacin