Tsuneo Yasuda (1), Takeshi Iwamoto (1), Masayuki Ohara (1), Seiji Sato
(1), Hideaki Kohri (1), Koichi Noguchi (2) and Emiko Senba (3)
(1) Nutrition Research Institute, Otsuka Pharmaceutical Factory, Inc., 115 Tateiwa, Muya-cho, Naruto, Tokushima 772-8601, Japan
(2) Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
(3) Department of Anatomy and Neurobiology, Wakayama Medical College, 811-1 Kimiidera, Wakayama 641-0012, Japan
Abstract: We investigated the effects of OT-7100, a novel analgesic compound (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimidine), on prostaglandin E2 biosynthesis in vitro, acute hyperalgesia induced by yeast and substance P in rats and hyperalgesia in rats with a chronic constriction injury to the sciatic nerve (Bennett model), which is a model for peripheral neuropathic pain. OT-7100 did not inhibit prostaglandin E2 biosynthesis at 10-8 - 10-4 M. Single oral doses of 3 and 10 mg/kg OT-7100 were effective on the hyperalgesia induced by yeast. Single oral doses of 0.1, 0.3, 1 and 3 mg/kg OT-7100 were effective on the hyperalgesia induced by substance P in which indomethacin had no effect. Repeated oral administration of OT-7100 (10 and 30 mg/kg) was effective in normalizing the mechanical nociceptive threshold in the injured paw without affecting the nociceptive threshold in the uninjured paw in the Bennett model. Indomethacin had no effect in this model. While amitriptyline (10 and 30 mg/kg) and clonazepam (3 and 10 mg/kg) significantly normalized the nociceptive threshold in the injured paw, they also increased the nociceptive threshold in the uninjured paw. These results suggest that OT-7100 is a new type of analgesic with the effect of normalizing the nociceptive threshold in peripheral neuropathic hyperalgesia.
Keywords: OT-7100, Chronic neuropathy, Hyperalgesia, Analgesic