Effects of YM175, a New-Generation Bisphosphonate, on Hypercalcemia Induced by Tumor-Derived Bone Resorbing Factors in Rats
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概要
- 論文の詳細を見る
YM175 (disodium cycloheptylaminomethylenediphosphonate monohydrate) is a new-generation bisphosphonate with stronger inhibitory activity on bone resorption than first-generation bisphosphonates. In the present study, the effect of YM175 on hypercalcemia induced in rats by single administration of either parathyroid hormone-related protein (PTHrP) or concomitant administration of PTHrP and interleukin 1β (IL-1β) was investigated. YM175 (0.01 – 1 mg/kg, i.v.) inhibited the increase in serum free calcium concentration induced by continuous administration of PTHrP alone (3 μg/rat/day, s.c., 7 days) dose-dependently. The inhibitory effect of YM175 appeared the day after administration and remained 3 days after administration. The effect of YM175 reached a maximum 2 days after administration, at which time the ED50 value of YM175 was calculated to be 0.041 mg/kg, i.v., revealing a potency approximately 50- and 10-fold stronger than those of either pamidronate or alendronate, respectively. In contrast, elcatonin (1 – 10 units/kg, s.c.) only transiently inhibited PTHrP-induced free calcium increase. YM175 (0.1 – 3 mg/kg, i.v.) also inhibited the increase in the serum free calcium concentration induced by continuous concomitant administration of both PTHrP and IL-1β in a dose-dependent manner. These results indicated that YM175 is expected to be a useful drug for hypercalcemia associated with malignant tumors due to its efficacy and range of effect.
- 社団法人 日本薬理学会の論文
著者
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Kokubo S
Yamanouchi Pharmaceutical Co. Ltd. Tsukuba City Jpn
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TAKAHASHI Koichiro
Applied Pharmacology Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yam
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SHIRAHATA Atsushi
Applied Pharmacology Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yam
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FUKUSHIMA Shinji
Applied Pharmacology Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yam
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KOKUBO Satoshi
Applied Pharmacology Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yam
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TERAMURA Kyoko
Applied Pharmacology Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yam
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USUDA Shinji
Applied Pharmacology Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yam
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Usuda S
Applied Pharmacology Research Pharmacology Laboratories Institute For Drug Discovery Research Yamano
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Usuda Shinji
Applied Pharmacology Laboratories Yamanouchi Pharmaceutical Co. Ltd.
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Teramura Kyoko
Applied Pharmacology Research Pharmacology Laboratories Institute For Drug Discovery Research Yamano
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Kokubo Satoshi
Applied Pharmacology Research Pharmacology Laboratories Institute For Drug Discovery Research Yamano
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Fukushima Shinji
Applied Pharmacology Research Pharmacology Laboratories Institute For Drug Discovery Research Yamano
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Shirahata Atsushi
Applied Pharmacology Research Pharmacology Laboratories Institute For Drug Discovery Research Yamano
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Takahashi Koichiro
Applied Pharmacology Laboratories Yamanouchi Pharmaceutical Co. Ltd.
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Takahashi Koichiro
Applied Pharmacology Research Pharmacology Laboratories Institute For Drug Discovery Research Yamano
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