2. Academic Validation
  3. Clodronate: A Vesicular ATP Release Blocker

Clodronate: A Vesicular ATP Release Blocker

  • Trends Pharmacol Sci. 2018 Jan;39(1):13-23. doi: 10.1016/j.tips.2017.10.007.
Yoshinori Moriyama 1,  Masatoshi Nomura 2
Affiliations

Affiliations

  • 1 Department of Biochemistry, Matsumoto Dental University, Shioziri 399-0781, Japan; Department of Membrane Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-0082, Japan. Electronic address: [email protected].
  • 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan. Electronic address: [email protected].
PMID: 29146440 DOI: 10.1016/j.tips.2017.10.007
Abstract

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.

Keywords

clodronate; ketone body; neuropathic pain; pregabalin; purinergic signaling; vesicular nucleotide transporter.

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