Norquetiapine

Norquetiapine is an active metabolite of the atypical antipsychotic quetiapine (Item No. 14152).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 (K_i = 3.5 nM), as well as the 5-HT receptor subtypes 5-HT₁, 5-HT₂, and 5-HT₇ (K_is = 45-1,117 nM). It also binds to α₁- and α₂-adrenergic, dopamine D₁-D₅, and M₁-M₅ muscarinic receptors (K_is = 95-736, 196-1,419, and 23-453 nM, respectively). It acts as an antagonist at histamine H₁, α_1A- and α_1D-adrenergic, as well as M₁, M₃, and M₅ muscarinic receptors, in a concentration-dependent manner and as an agonist at the 5-HT_1A 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.

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1. Jensen, N.H., Rodriguiz, R.M., Caron, M.G., et al. N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT_1A agonist, as a putative mediator of quetiapine’s antidepressant activity. Neuropsychopharmacology 33(10), 2303-2312 (2008).