The Profile of FR140423, a Novel Anti-inflammatory Compound, in Yeast-Induced Rat Hyperalgesia
Access this Article
Search this Article
The mechanism of action of FR140423 (3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole), a novel anti-inflammatory compound, in a rat yeast-induced hyperalgesic model was investigated and compared with those of indomethacin and morphine. We tested the inhibitory effects of FR140423 on the formation of arachidonic acid metabolites, prostaglandin (PG) E<SUB>2</SUB>, thromboxane (TX) B<SUB>2</SUB> and leukotriene (LT) B<SUB>4</SUB>, in yeast-injected inflamed paws and the effect of the opioid receptor antagonist naloxone on FR140423-induced anti-hyperalgesic effect and inhibition of the formation of arachidonic acid metabolites. Oral administration of FR140423 showed a dose-dependent anti-hyperalgesic effect. This effect was fourfold more potent than that of indomethacin but less potent than that of morphine. Unlike morphine, FR140423 suppressed the levels of PGE<SUB>2</SUB> and TXB<SUB>2</SUB> but not LTB<SUB>4</SUB> in inflamed paws. FR140423 did not inhibit yeast-induced paw edema. The anti-hyperalgesic effect of FR140423 in yeast-injected rat paws was partially blocked by naloxone. However, the inhibitory effects of FR140423 on the formation of PGE<SUB>2</SUB> and TXB<SUB>2</SUB> in yeast-injected rat paws were not antagonized by naloxone. These results suggest that FR140423 shows a potent anti-hyperalgesic effect mediated by inhibition of PGs in inflamed tissue and by activation of opioid receptors.
- The Japanese Journal of Pharmacology
The Japanese Journal of Pharmacology 81(1), 94-98, 1999-09
The Japanese Pharmacological Society