ANTINOCICEPTIVE ACTIONS OF R(-)-FLURBIPROFEN - A NONCYCLOOXYGENASE 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 E(2) 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.