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

Aaron N. Snead; Motonori Miyakawa; Edwin S. Tan; Thomas S. Scanlan

doi:10.1016/j.bmcl.2008.08.013

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

Aaron N. Snead, Motonori Miyakawa, Edwin S. Tan, Thomas S. Scanlan

Chemical Physiology and Biochemistry

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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 (TAAR₁). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance.

Original language	English (US)
Pages (from-to)	5920-5922
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2008.08.013
State	Published - Nov 15 2008

Keywords

Amiodarone
G protein-coupled receptors
TAAR
Trace amine-associated receptor 1

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2008.08.013

Cite this

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title = "Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites",

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 (TAAR1). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance.",

keywords = "Amiodarone, G protein-coupled receptors, TAAR, Trace amine-associated receptor 1",

author = "Snead, {Aaron N.} and Motonori Miyakawa and Tan, {Edwin S.} and Scanlan, {Thomas S.}",

note = "Funding Information: We thank the David K. Grandy Lab for the donation of the r-hTAAR 1 cell line. This work was supported by fellowship from the Ford Foundation (A.N.S.), and a grant from the National Institutes of Health (DK52798, T.S.S.). ",

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AU - Snead, Aaron N.

AU - Miyakawa, Motonori

AU - Tan, Edwin S.

AU - Scanlan, Thomas S.

N1 - Funding Information: We thank the David K. Grandy Lab for the donation of the r-hTAAR 1 cell line. This work was supported by fellowship from the Ford Foundation (A.N.S.), and a grant from the National Institutes of Health (DK52798, T.S.S.).

PY - 2008/11/15

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N2 - 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 (TAAR1). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance.

AB - 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 (TAAR1). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance.

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