title: Lipoic-based TRPA1/TRPV1 antagonist to treat orofacial pain.
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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gualdani
authors.affiliation: ∥Lab of Molecular and Cell. Pharm. Purinergic Transmission, Department of Pharmacological Biomol. Sciences (DiSFeB), University of Milan, 20122 Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ceruti
authors.affiliation: ∥Lab of Molecular and Cell. Pharm. Purinergic Transmission, Department of Pharmacological Biomol. Sciences (DiSFeB), University of Milan, 20122 Milan, Italy.|⊥Department of Drug Discovery and Development, Italian Institute of Technology (IIT), 16163 Genova, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Magni
authors.affiliation: ∥Lab of Molecular and Cell. Pharm. Purinergic Transmission, Department of Pharmacological Biomol. Sciences (DiSFeB), University of Milan, 20122 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Merli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.forename: Oscar
authors.initials: O
authors.lastname: Francesconi
authors.forename: Barbara
authors.initials: B
authors.lastname: Richichi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Moncelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D016466:CHO Cells; D015220:Calcium Channels / Q000235:genetics; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005157:Facial Pain / Q000139:chemically induced / Q000188:drug therapy*; D005904:Glial Fibrillary Acidic Protein; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D018408:Patch-Clamp Techniques; D051381:Rats; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use*; D014162:Transfection; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D015220:Calcium Channels; D005904:Glial Fibrillary Acidic Protein; D017879:Isothiocyanates; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; C486577:Trpv4 protein, rat; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D008063:Thioctic Acid
keywords: Lipoic acid; TRP channels; antiallodynic agents; trigeminal pain