Clodronate: A Vesicular ATP Release Blocker
Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VNUT), a transporter responsible for vesicular storage of ATP. Clodronate inhibits vesicular ATP release from neurons and reduces chronic neuropathic and inflammatory pain following blockade of purinergic chemical transmission. Its effectiveness is stronger, faster acting, and longer lasting than that of existing drugs such as pregabalin. Thus, clodronate might be a promising drug for attenuating chronic neuropathic pain and opens a new field of drug discovery as a presynaptic blocker for purinergic chemical transmission.
Publisher URL: http://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(17)30202-X
DOI: 10.1016/j.tips.2017.10.007
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