4-hydroxyatomoxetine

4-hydroxyatomoxetine is the **major active metabolite** of atomoxetine, which is itself a selective norepinephrine reuptake inhibitor used for the treatment of attention deficit hyperactivity disorder (ADHD). This metabolite is generated primarily via CYP2D6-mediated hydroxylation of atomoxetine and rapidly undergoes glucuronidation to form the inactive 4-hydroxyatomoxetine-glucuronide. 4-hydroxyatomoxetine displays unique pharmacology relative to the parent drug: - It acts as an **antagonist at the μ-opioid receptor**, a **partial agonist at the κ-opioid receptor**, and shows moderate affinity for the δ-opioid receptor. - Like atomoxetine, 4-hydroxyatomoxetine retains activity at the norepinephrine transporter (NET), albeit with slightly reduced affinity, and has weak activity at the serotonin transporter (SERT). - The metabolite also binds, with lower affinity than atomoxetine, to other targets such as GABA-A, α-adrenergic, histamine H1 receptors, and NMDA receptors. The metabolite contributes to the pharmacological effects in extensive metabolizers but is found at a much lower concentration in the plasma than atomoxetine itself. 4-hydroxyatomoxetine is not approved for any indication as a standalone drug and serves primarily as a biomarker and contributor to atomoxetine's therapeutic and adverse effect profile[1][2][3][4].

Other names

4-OH-ATX3-methyl-4-[(1R)-3-(methylamino)-1-phenylpropoxy]phenol