Lipoic-based TRPA1/TRPV1 antagonist to treat orofacial pain

ACS Chem Neurosci. 2015 Mar 18;6(3):380-5. doi: 10.1021/cn500248u. Epub 2015 Jan 6.

Abstract

Inflammation of the trigeminal nerve is considered one of the most painful conditions known to humankind. The diagnosis is often difficult; moreover, safe and effective pharmacological treatments are lacking. A new molecule, ADM_12, formed by a lipoic and omotaurine residues covalently linked, is here reported. In vitro and in vivo tests showed that ADM_12 is a very attractive original compound presenting (i) a remarkable safety profile; (ii) a high binding constant versus TRPA1; (iii) an intriguing behavior versus TRPV1; and (iv) the ability to significantly and persistently reduce mechanical facial allodynia in rats. Noteworthy, by testing ADM_12, we shed light on the unprecedented involvement of TRPA1 and TRPV1 channels in orofacial pain.

Keywords: Lipoic acid; TRP channels; antiallodynic agents; trigeminal pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / therapeutic use*
  • CHO Cells
  • Calcium Channels / genetics
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Facial Pain / chemically induced
  • Facial Pain / drug therapy*
  • Glial Fibrillary Acidic Protein
  • Humans
  • Isothiocyanates / pharmacology
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / genetics
  • Patch-Clamp Techniques
  • Rats
  • TRPA1 Cation Channel
  • TRPV Cation Channels / metabolism
  • Thioctic Acid / therapeutic use*
  • Transfection
  • Transient Receptor Potential Channels / antagonists & inhibitors*
  • Transient Receptor Potential Channels / genetics

Substances

  • Anti-Inflammatory Agents
  • Calcium Channels
  • Glial Fibrillary Acidic Protein
  • Isothiocyanates
  • Nerve Tissue Proteins
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • Transient Receptor Potential Channels
  • Trpv4 protein, rat
  • 2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate
  • Thioctic Acid