Minodronic acid, a third-generation bisphosphonate, antagonizes purinergic P2X(2/3) receptor function and exerts an analgesic effect in pain models

The P2X(2/3) receptor has an important role in the nociceptive transmission. Minodronic acid is a third third-generation bisphosphonate and a potent inhibitor of bone resorption. We found that minodronic acid inhibited alpha,beta-methylene ATP-induced cation uptake with the potency higher than that...

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Bibliographic Details
Published in:European journal of pharmacology 2008-07, Vol.589 (1-3), p.98
Main Authors: Kakimoto, Shuichiro, Nagakura, Yukinori, Tamura, Seiji, Watabiki, Tomonari, Shibasaki, Kumiko, Tanaka, Shohei, Mori, Masamichi, Sasamata, Masao, Okada, Masamichi
Format: Article
Language:English
Subjects:
Acetic Acid
Adenosine Triphosphate - analogs & derivatives
Analgesics, Non-Narcotic - administration & dosage
Analgesics, Non-Narcotic - pharmacology
Animals
Bone Density Conservation Agents - administration & dosage
Bone Density Conservation Agents - pharmacology
CHO Cells
Cricetinae
Cricetulus
Diphosphonates - administration & dosage
Diphosphonates - pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Formaldehyde
Imidazoles - administration & dosage
Imidazoles - pharmacology
Injections, Subcutaneous
Male
Mice
Mice, Inbred ICR
Pain - chemically induced
Pain - metabolism
Pain - prevention & control
Pain Measurement
Purinergic P2 Receptor Antagonists
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2X2
Receptors, Purinergic P2X3
Time Factors
Transfection
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Summary:The P2X(2/3) receptor has an important role in the nociceptive transmission. Minodronic acid is a third third-generation bisphosphonate and a potent inhibitor of bone 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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2008.05.011