Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect.
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.
Creighton
Christopher J
CJ
Drug Discovery, Johnson and Johnson Pharmaceutical, Research and Development, Spring House, PA 19477-0776, USA. ccreight@prdus.jnj.com
Ramabadran
Kris
K
Ciccone
Patrick E
PE
Liu
Jingchun
J
Orsini
Michael J
MJ
Reitz
Allen B
AB
D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D006801:Humans; D011437:Propylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013329:Structure-Activity Relationship
D011437:Propylamines; D017473:Receptors, Opioid, kappa; D000069445:Atomoxetine Hydrochloride