Antinociceptive actions of R(-)-flurbiprofen--a non-cyclooxygenase inhibiting 2-arylpropionic acid--in rats.
Intraperitoneal administration of R(-)- and S(+)-flurbiprofen resulted in dose dependent antinociceptive behavior in the rat paw formalin test. S(+)-flurbiprofen was significantly more potent than the non-cyclooxygenase inhibiting R(-)-enantiomer with a potency ratio of about 3 to 1. Chiral inversion was very low and does not seem to account for the action of R(-)-flurbiprofen. In a modified Randall Selitto assay also both enantiomers were active in a dose dependent manner following systemic administration. Following local administration into the inflamed paw only S(+)-flurbiprofen showed significant dose related antinociceptive effects. R(-)-flurbiprofen was unable to block prostaglandin E2 induced hyperalgesia following local administration. Consequently, a central site of action independent of prostaglandin synthesis inhibition has to be discussed with respect to antinociceptive activity following systemic administration.
Geisslinger
G
G
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Ferreira
S H
SH
Menzel
S
S
Schlott
D
D
Brune
K
K
D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005480:Flurbiprofen / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D005528:Foot; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007536:Isomerism; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000700:Analgesics; D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen