Masako Uchii, Miyuki Takashima, Tomomi Sugiyama and Nobuo Kosaka
General Pharmacology, Drug Discovery Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan
Abstract: The purpose of this study was to evaluate the effects of 3-[bis(4-hydroxyphenyl)methyl]-2-[4-(2-chlorophenyl)-piperazin-1-ylcarbonyl]-1-(2-dimethylaminoethyl) indole methanesulfonate (KW-8232), a novel anti-osteoporotic agent, on bone loss in neurectomized rats. We also investigated the effect of KW-8232 on bone resorption in this animal model. Male Sprague-Dawley rats underwent unilateral hind-limb immobilization by sciatic neurectomy. KW-8232 (3, 10 and 30 mg/kg, p.o.) was effective in inhibiting femoral bone loss. KW-8232 decreased urinary pyridinoline and deoxypyridinoline excretion. These results indicate that KW-8232 effectively prevents the bone loss due to immobilization.
Keywords: KW-8232, Bone loss, Sciatic neurectomy