Mode of analgesic action of dipyrone: direct antagonism of inflammatory hyperalgesia.
Dipyrone blocked carrageenin-induced oedema and hyperalgesia in a dose-dependent manner. In contrast with indomethacin, paracetamol and acetyl salicylic acid, much lower doses of dipyrone were necessary for blocking hyperalgesia (ED50 = 19 mg/kg, i.p.) than oedema (180 mg/kg, i.p.) Dipyrone administered intraperitonially or intraplantarly was able to antagonise PGE2-, isoprenaline- and calcium chloride-induced hyperalgesia, effects which are not observed with non-steroid anti-inflammatory drugs. Systemic or local administration of dipyrone had no effect upon Db-cAMP-induced hyperalgesia while a centrally acting analgesic, morphine, given systemically, was highly effective. These results support our suggestion that the mechanism of action of dipyrone is different from that of classical non-steroidal anti-inflammatory drugs. Although the site of action is peripheral its analgesic effect does not derive from inhibition of the synthesis of prostaglandins but is exerted via direct blockade of the inflammatory hyperalgesia.
D000082:Acetaminophen / Q000494:pharmacology; D000632:Aminopyrine / Q000031:analogs & derivatives*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003994:Bucladesine; D002351:Carrageenan; D015232:Dinoprostone; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D006941:Hyperesthesia / Q000188:drug therapy*; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol; D008297:Male; D011458:Prostaglandins E; D051381:Rats; D011919:Rats, Inbred Strains
D000700:Analgesics; D011458:Prostaglandins E; D000632:Aminopyrine; D000082:Acetaminophen; D003994:Bucladesine; D004177:Dipyrone; D002351:Carrageenan; D015232:Dinoprostone; D007545:Isoproterenol; D001241:Aspirin; D007213:Indomethacin