Antinociceptive activity of filenadol on inflammatory pain.
The novel analgesic filenadol (d, 1-erythro-1-(3',4'-methylenedioxyphenyl)-1- morpholinopropan-2-ol) inhibited phenyl-p-benzoquinone-induced writhing in mice with ID50 values of 68.8 (p.o.), 1.67 (i.v.) and 0.48 (i.c.v.) mg/kg. Hyperalgesia induced by arachidonic acid, PGE2 or LTB4 in this test was also decreased by filenadol (ID50 = 24.4, 3.7 and 50.1 mg/kg p.o., respectively). This compound was effective on PGE2, LTB4, bradykinin, PAF or IL-1 beta-induced decrease in pain threshold in the rat paw pressure model and almost totally suppressed the writhing induced by zymosan in mice, while peritoneal production of 6-ketoPGF1 alpha was inhibited by 48.5-62% and only at 100 mg/kg significant inhibition of LTC4 was achieved. The late phase of formalin-induced pain response in mice was prevented by filenadol, without affecting the oedema. Filenadol is an antinociceptive agent that reduces the hyperalgesic effects of inflammatory mediators besides inhibiting partially the synthesis of eicosanoids.
Bustos
G
G
Department of Pharmacology, University of Valencia, Spain.
Ferrándiz
M L
ML
Sanz
M J
MJ
Payá
M
M
Alcaraz
M J
MJ
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016227:Benzoquinones; D003061:Codeine / Q000494:pharmacology; D005557:Formaldehyde; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015054:Zymosan
D000700:Analgesics; D016227:Benzoquinones; D009025:Morpholines; D005557:Formaldehyde; D015054:Zymosan; D003061:Codeine; D007213:Indomethacin; C095703:filenadol