Abstract
The analgesic and anti-inflammatory activities of Y-23023, a new nonsteroidal analgesic and antiinflammatory compound, were investigated in acute, subacute and chronic pain models in rats. In the carrageenin paw edema test, Y-23023 (0.3 ?? 3 mg/kg, p.o.) dose-dependently inhibited hyperalgesia assessed by the Randall-Selitto method and paw edema. Y-23023 (1 mg/kg, p.o.), when administered at 2 hr after carrageenin injection, significantly elevated the reduced pain threshold without affecting paw edema. Therefore, the antinociception activity induced by Y23023 was not the result of its anti-inflammatory activity. In addition, Y-23023-induced antinociception was resistant to post-treatment with naloxone (2 mg/kg, s.c.), but was antagonized by intraplantar injection of prostaglandin E2 (1 μg/paw). These results suggest that Y-23023 produces a peripheral analgesic effect mediated by inhibition of prostaglandin production. Y-23023 (0.3 ?? 10 mg/kg, p.o.) also had a potent inhibitory effect on the silver nitrate-induced arthritic pain. In supressing acute and subacute pain, Y-23023 was more potent than diclofenac sodium, indomethacin and loxoprofen sodium. The analgesic and anti-inflammatory activities of Y23023 (0.1 ?? 1 mg/kg/day, p.o.) on the adjuvant-induced hyperalgesia and the paw swelling were nearly equipotent to diclofenac sodium and indomethacin, but were more potent than loxoprofen sodium. Therefore, Y-23023 would be regarded to show predominantly strong analgesic activity in acute and subacute pain when compared with reference drugs. The above results suggest that Y-23023 is a novel analgesic compound with an anti-inflammatory activity in the clinical field.
