Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect

Christopher J Creighton; Kris Ramabadran; Patrick E Ciccone; Jingchun Liu; Michael J Orsini; Allen B Reitz

doi:10.1016/j.bmcl.2004.05.018

Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect

Bioorg Med Chem Lett. 2004 Aug 2;14(15):4083-5. doi: 10.1016/j.bmcl.2004.05.018.

Authors

Christopher J Creighton¹, Kris Ramabadran, Patrick E Ciccone, Jingchun Liu, Michael J Orsini, Allen B Reitz

Affiliation

¹ Drug Discovery, Johnson and Johnson Pharmaceutical, Research and Development, Spring House, PA 19477-0776, USA. [email protected]

PMID: 15225731
DOI: 10.1016/j.bmcl.2004.05.018

Abstract

The major human metabolite of atomoxetine (4-hydroxyatomoxetine) was tested against a panel of receptors and enzymes, and was found to interact with the mu, delta, and kappa-opioid receptors based upon studies involving both binding and functional assays. 4-hydroxyatomoxetine was determined to be a partial agonist of the kappa-opioid receptor.

MeSH terms

Atomoxetine Hydrochloride
Attention Deficit Disorder with Hyperactivity / drug therapy
Humans
Propylamines / chemical synthesis*
Propylamines / pharmacokinetics*
Propylamines / pharmacology
Receptors, Opioid, kappa / agonists*
Structure-Activity Relationship

Substances

Propylamines
Receptors, Opioid, kappa
Atomoxetine Hydrochloride