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this just in on atomoxetine » SLS

Posted by zeugma on August 8, 2004, at 10:01:05

In reply to Re: some people just don't do well with norepinephrine, posted by SLS on August 7, 2004, at 13:26:44

I was the poster who brought up the atomoxetine-nortriptyline contrast. Atomoxetine's major metabobolite, 4-hydroxyatomoxetine, is a kappa-opiate partial agonist:

1: Bioorg Med Chem Lett. 2004 Aug 2;14(15):4083-5. Related Articles, Links


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

Creighton CJ, Ramabadran K, Ciccone PE, Liu J, Orsini MJ, Reitz AB.

Drug Discovery, Johnson and Johnson Pharmaceutical, Research and Development, Spring House, PA 19477-0776, USA. ccreight@prdus.jnj.com

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.


Dysphoria is a frequent response to kappa partial agonists. This metabolite could be responsible for the fatigue, and potential induction of depression, by atomoxetine.


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