Geisslinger G, Ferreira S H, Menzel S, Schlott D, Brune K
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Life Sci. 1994;54(10):PL173-7. doi: 10.1016/0024-3205(94)00555-9.
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.
在大鼠爪部福尔马林试验中，腹腔注射R(-)-和S(+)-氟比洛芬可产生剂量依赖性的抗伤害感受行为。S(+)-氟比洛芬的效力明显高于非环氧化酶抑制性的R(-)-对映体，效力比约为3比1。手性转化非常低，似乎不能解释R(-)-氟比洛芬的作用。在改良的Randall Selitto试验中，全身给药后两种对映体也均呈剂量依赖性活性。仅在向发炎爪部局部给药后，S(+)-氟比洛芬显示出显著的剂量相关抗伤害感受作用。局部给药后，R(-)-氟比洛芬无法阻断前列腺素E2诱导的痛觉过敏。因此，对于全身给药后的抗伤害感受活性，必须讨论一个独立于前列腺素合成抑制的中枢作用位点。
