Norquetiapine is an active metabolite of the atypical antipsychotic quetiapine .1 It is formed from quetiapine primarily by the cytochrome P450 (CYP) isoform CYP3A4. Norquetiapine selectively inhibits the norepinephrine transporter (NET; IC50 = 12 nM) over the serotonin (5-HT) and dopamine transporters (SERT and DAT; IC50s = 988 and >10,000 nM, respectively). It binds to the histamine H1 receptor (Ki = 3.5 nM), as well as the 5-HT receptor subtypes 5-HT1, 5-HT2, and 5-HT7 (Kis = 45-1,117 nM). It also binds to α1- and α2-adrenergic, dopamine D1-D5, and M1-M5 muscarinic receptors (Kis = 95-736, 196-1,419, and 23-453 nM, respectively). It acts as an antagonist at histamine H1, α1A- and α1D-adrenergic, as well as M1, M3, and M5 muscarinic receptors, in a concentration-dependent manner and as an agonist at the 5-HT1A receptor (EC50 = 4,898 nM). Norquetiapine (0.1, 0.5, and 1 mg/kg) reduces increases in immobility time in mice heterozygous for the gene encoding vesicular monoamine transporter 2 (Vmat2) but not in wild-type mice.
1.Jensen, N.H., Rodriguiz, R.M., Caron, M.G., et al.N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine’s antidepressant activityNeuropsychopharmacology33(10)2303-2312(2008)