Minodronic acid, a third-generation bisphosphonate, antagonizes purinergic P2X2/3 receptor function and exerts an analgesic effect in pain models

被引：29

作者：

Kakimoto, Shuichiro ^{[1
]}

Nagakura, Yukinori ^{[1
]}

Tamura, Seiji ^{[1
]}

Watabiki, Tomonari ^{[1
]}

Shibasaki, Kumiko ^{[1
]}

Tanaka, Shohei ^{[1
]}

Mori, Masamichi ^{[1
]}

Sasamata, Masao ^{[1
]}

Okada, Masamichi ^{[1
]}

机构：

[1] Astellas Pharma Inc, Drug Discovery Res, Pharmacol Res Labs, Dept Neurosci, Tsukuba, Ibaraki 3058585, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2008年 / 589卷 / 1-3期

关键词：

bisphosphonate; minodronic acid; P2X(2/3) receptor; analgesia; pain;

D O I：

10.1016/j.ejphar.2008.05.011

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The P2X(2/3) receptor has an important role in the nociceptive transmission. Minodronic acid is a third third-generation bisphosphonate and a potent inhibitorofbone resorption. We found that minodronic acid inhibited alpha,beta-methylene ATP-induced cation uptake with the potency higher than that of suramin in the P2X(2/3) receptor receptor-expressing cells. Other bisphosphonates did not show such activity. Subcutaneously administered (10-50 mg/kg) minodronic acid significantly inhibited the alpha,beta-methylene ATP-, acetic acid- and formalin-induced nociceptive behaviors in mice. These unique effects of minodronic acid would be beneficial for the treatment of accelerated bone turnover diseases accompanied by bone pain, including bone metastases. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：98 / 101

页数：4

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