Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites

  • Bioorg Med Chem Lett. 2008 Nov 15;18(22):5920-2. doi: 10.1016/j.bmcl.2008.08.013.
Aaron N Snead  1 ,  Motonori Miyakawa ,  Edwin S Tan ,  Thomas S Scanlan
Affiliations
  • 1. Graduate Program in Chemistry and Chemical Biology, University of California at San Francisco, 600 16th Street, San Francisco, CA 94143, USA.
PMID: 18752950 DOI: 10.1016/j.bmcl.2008.08.013
Abstract

Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites the iodothyronamines. Several of these amiodarone derivatives act as specific agonists of the G protein-coupled receptor (GPCR) trace amine-associated receptor 1 (TAAR(1)). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance.