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Clodronate: A Vesicular ATP Release Blocker.

Yoshinori Moriyama1, Masatoshi Nomura2

  • 1Department 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.

Trends in Pharmacological Sciences
|November 18, 2017
PubMed
Summary

Clodronate effectively treats chronic pain by inhibiting vesicular nucleotide transporter (VNUT), blocking ATP release from neurons. This bisphosphonate offers a potent, fast-acting alternative for neuropathic pain management.

Keywords:
clodronateketone bodyneuropathic painpregabalinpurinergic signalingvesicular nucleotide transporter

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Management

Background:

  • Clodronate, a bisphosphonate, is widely used for osteoporosis treatment.
  • Its analgesic mechanism and efficacy remained unclear until recently.
  • Osteoporosis treatments often lack effective pain management components.

Purpose of the Study:

  • To elucidate the mechanism of clodronate's analgesic effects.
  • To identify clodronate as a selective inhibitor of the vesicular nucleotide transporter (VNUT).
  • To evaluate clodronate's efficacy in managing chronic neuropathic and inflammatory pain.

Main Methods:

  • Investigated clodronate's interaction with the vesicular nucleotide transporter (VNUT).
  • Assessed the impact of VNUT inhibition on ATP release from neurons.
  • Compared the efficacy of clodronate with existing pain medications like pregabalin in preclinical models.

Main Results:

  • Clodronate was identified as a potent and selective inhibitor of VNUT.
  • Inhibition of VNUT by clodronate effectively reduced vesicular ATP release from neurons.
  • Clodronate demonstrated superior effectiveness, faster onset, and longer duration compared to pregabalin in alleviating chronic neuropathic and inflammatory pain.

Conclusions:

  • Clodronate's analgesic action is mediated by the blockade of purinergic chemical transmission via VNUT inhibition.
  • Clodronate presents a promising therapeutic agent for attenuating chronic neuropathic pain.
  • This discovery opens new avenues for drug development targeting presynaptic purinergic signaling.