Hiroko Kido (1), Naofumi Murakami(1), Atsuko Ito (1), Kazuo Kimura (1),
Nobuo Kodera (2), Takaaki Doi (2) and Tomohiro Naruse (1)
(1) Research & Development Laboratories, Maruho Co., Ltd., 1-8-23 Oyodo Naka, Kita-ku, Osaka 531, Japan
(2) Hikone Research Laboratories, Maruho Co., Ltd., 2763 Takamiya-cho, Hikone, Shiga 522 -02, Japan
Abstract: Anti-inflammatory, analgesic and anti-pyretic effects of d-2-[4-(3-methyl-2-thienyl)phenyl] propionic acid (M-5011), a new non-steroidal anti-inflammatory drug (NSAID), were compared with those of indomethacin, diclofenac sodium and ketoprofen in rats and guinea pigs. Anti-inflammatory effect of M-5011 on ultraviolet-induced erythema in guinea pigs was 11.7 and 1.8 times more potent than that of indomethacin and ketoprofen, respectively. Inhibitory effect of M-5011 on carrageenin-induced paw edema was 2 and 1.5 times more potent than that of indomethacin and diclofenac sodium, respectively. Analgesic effect of M-5011 on dry yeast-induced hyperalgesia or adjuvant-induced arthritic pain was equipotent to that of indomethacin, diclofenac sodium or ketoprofen. Anti-pyretic effect of M-5011 on yeast-induced pyrexia in rats was 4.2 and 4.6 times more potent than that of indomethacin and ketoprofen, respectively. Inhibitory effect of M-5011 on prostaglandin E2 production in the exudate of air-pouch inflammation induced by carrageenin was 1.75 times more potent than that in the non-inflamed site (stomach). As a result, gastric ulcerogenic activity of M-5011 was half that of indomethacin in rat. These results suggest that M-5011 shows more potent anti-inflammatory and anti-pyretic effects and equipotent analgesic effect with low gastro-ulcerogenic activity compared with classical NSAIDs.
Keywords: M-5011, Non-steroidal anti-inflammatory drug, Ulcerogenic activity