(+-)-O-Desmethyl Venlafaxine

(+-)-O-Desmethyl venlafaxine is an active metabolite of the selective norepinephrine and serotonin reuptake inhibitor (SNRI) venlafaxine.{32153} It is formed from venlafaxine by the cytochrome P450 (CYP) isoform CYP2D6.{32155} Desvenlafaxine inhibits the norepinephrine transporter (NET) and serotonin transporter (SERT) with IC50 values of 47.3 and 531.3 nM, respectively, for the human transporters.{32153} It is selective for NET and SERT over 50 receptors, peptides, and ion channels among others. It increases extracellular norepinephrine (NE) in the male rat hypothalamus and increases extracellular serotonin (5-HT) in the same region when used in combination with the 5-HT1A receptor antagonist WAY-100635 (Item No. 14599). Desvenlafaxine (3 mg/kg per day) reduces immobility time in the forced swim test in a rat model of cognitive deficits and depression induced by myocardial infarction (MI) when compared with MI-vehicle control animals 16 weeks following MI.{48908} It also improves learning in the passive avoidance step-down test two weeks following MI compared to MI-vehicle control rats and spatial memory in the Morris water maze 16 weeks following MI.