[Effect of KW-8232 on bone turnover in ovariectomized rats].
The effects of 3-[bis(4-hydroxyphenyl)methyl]-2-[4-(2-chlorophenyl)- piperazin-1-ylcarbonyl]-1-(2-dimethylamino ethyl) indole methanesulfonate (KW-8232) on the bone turnover in ovariectomized (OVX) rats were studied by the oral administration for 6 weeks. KW-8232 inhibited the decreased bone mineral densities of the femur and tibia in OVX rats. OVX induced the increase of serum alkaline phosphatase and osteocalcin levels, markers of high bone turnover, and also increased urinary hydroxyproline, pyridinoline and deoxypyridinoline excretion, markers of bone resorption. KW-8232 significantly inhibited the increase of serum alkaline phosphatase level at doses of 10 and 30 mg/kg and the increase of osteocalcin level at a dose of 3 mg/kg. KW-8232 (1 mg/kg) markedly suppressed the OVX-induced increase of urinary hydroxyproline, pyridinoline and deoxypyridinoline excretion. KW-8232 didn't affect serum calcium level, but significantly decreased urinary calcium excretion at doses of 10 and 30 mg/kg. These results suggest that KW-8232 decreased bone loss in this model by suppressing bone resorption.
Uchii
M
M
Drug Discovery Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Takashima
M
M
Sugiyama
T
T
Kosaka
N
N
D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008698:Mesylates / Q000494:pharmacology* / Q000627:therapeutic use; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D007211:Indoles; C116436:KW 8232; D008698:Mesylates; D015675:Osteocalcin; C015484:pyridinoline; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium