title: [Analgesic and anti-inflammatory effect of (+/-)-N,N- dimethylcarbamoylmethyl 2-[7-(2-methyl-5H-[1] benzopyrano [2,3-b] pyridyl)] propionate (Y-23023), a new non-steroidal anti-inflammatory drug].
abstract: The analgesic and anti-inflammatory activities of Y-23023, a new nonsteroidal analgesic and anti-inflammatory 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 Y-23023 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 microgram/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 suppressing acute and subacute pain, Y-23023 was more potent than diclofenac sodium, indomethacin and loxoprofen sodium. The analgesic and anti-inflammatory activities of Y-23023 (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.
authors.affiliation: Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwahisa
authors.forename: Y
authors.initials: Y
authors.lastname: Yasunaga
authors.forename: H
authors.initials: H
authors.lastname: Ochi
authors.forename: M
authors.initials: M
authors.lastname: Matsuura
authors.forename: T
authors.initials: T
authors.lastname: Imayoshi
authors.forename: M
authors.initials: M
authors.lastname: Terasawa
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001578:Benzopyrans / Q000627:therapeutic use*; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D011725:Pyridines; C063558:N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-1-benzopyrano(2,3-b)pyridine-7-acetate; D002351:Carrageenan