title: The alpha2-delta protein: an auxiliary subunit of voltage-dependent calcium channels as a recognized drug target.
abstract: Currently, there are two drugs on the market, gabapentin (Neurontin) and pregabalin (Lyrica), that are proposed to exert their therapeutic effect through binding to the alpha2-delta subunit of voltage-sensitive calcium channels. This activity was unexpected, as the alpha2-delta subunit had previously been considered not to be a pharmacological target. In this review, the role of the alpha2-delta subunits is discussed and the mechanism of action of the alpha2-delta ligands in vitro and in vivo is summarized. Finally, new insights into the mechanism of drugs that bind to this protein are discussed.
authors.affiliation: Pfizer Inc, US Medical Affairs, New York, NY 10017, USA. andrew.thorpe@pfizer.com
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thorpe
authors.forename: James
authors.initials: J
authors.lastname: Offord
mesh_terms: D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D000077206:Gabapentin; D023281:Genomics; D006801:Humans; D008954:Models, Biological; D000069583:Pregabalin; D021122:Protein Subunits / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000588:Amines; C425903:CACNA2D1 protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D021122:Protein Subunits; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin