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

The P2X2/3 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 α,β-methylene ATP-induced cation uptake with the potency higher than that of suramin in the P2X2/3 receptor receptor-expressing cells. Other bisphosphonates did not show such activity. Subcutaneously administered (10–50 mg/kg) minodronic acid significantly inhibited the α,β-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.