A new mechanism of action of dipyrone: blockade of the release of a nociceptive factor from macrophages.
Rat macrophage monolayers pre-treated with endotoxin release into the incubating fluid a factor (MW greater than 10,000) capable of inducing writhing in mice (MNF). This release was inhibited by dipyrone (3.5-35 micrograms/ml) but not by indomethacin (0.5-2 micrograms/ml). Writhing in mice induced by the factor is blocked by dipyrone (0.5-50 mg/kg) and indomethacin (0.5-2 mg/kg). These results indicate that in addition to the previously described direct blockade of hyperalgesia by dipyrone, this drug may also affect the release of MNF, which induces in vivo nociception through the release of prostaglandin-like substances.
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Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade São Paulo, Brasil.
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D000632:Aminopyrine / Q000031:analogs & derivatives*; D000818:Animals; D004177:Dipyrone / Q000494:pharmacology*; D004926:Escherichia coli; D006930:Hyperalgesia / Q000209:etiology; D007213:Indomethacin / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D012640:Seizures / Q000139:chemically induced
D000632:Aminopyrine; D004177:Dipyrone; D007213:Indomethacin