Effect of KW-8232, a novel anti-osteoporotic agent, on bone loss in sciatic neurectomized rats.
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.
Uchii
M
M
General Pharmacology, Drug Discovery Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Takashima
M
M
Sugiyama
T
T
Kosaka
N
N
D000596:Amino Acids / Q000652:urine; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000652:urine; D003404:Creatinine / Q000652:urine; D005269:Femur / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008698:Mesylates / Q000494:pharmacology* / Q000627:therapeutic use; D010024:Osteoporosis / Q000517:prevention & control; D010710:Phosphates / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology* / Q000601:surgery
D000596:Amino Acids; D007211:Indoles; C116436:KW 8232; D008698:Mesylates; D010710:Phosphates; C015484:pyridinoline; C036020:deoxypyridinoline; D003404:Creatinine; D002118:Calcium