Trimipramine-d3 (maleate)

Trimipramine-d₃ (maleate) is intended for use as an internal standard for the quantification of trimipramine (maleate) by GC- or LC-MS. Trimipramine is a tricyclic antidepressant.^1,2,3 It selectively binds the serotonin (5-HT) transporter (SERT) over the norepinephrine transporter (NET) and dopamine transporter (DAT; K_ds = 149, 2,450, and 3,780 nM, respectively) and acts as a histamine H₁ receptor antagonist (K_i = 0.02 µM) that is selective for histamine H₁ over H₂, H₃, and H₄ receptors (K_is = 0.04, >100, and 43.6 µM, respectively).^1,2 Trimipramine binds to muscarinic acetylcholine and α₁- and α₂-adrenergic receptors (K_ds = 58, 24, and 580 nM, respectively), as well as dopamine D₁ and D₂ receptors and 5-HT receptor subtypes 5-HT_1C and 5-HT₂ (K_is = 346.7, 57.5, 537, and 19.5 nM, respectively).^1,3 It reduces immobility time in the forced swim test in rats when administered at a dose of 10 mg/kg.⁴ Formulations containing trimipramine have previously been used in the treatment of depression.

1.Richelson, E., and Nelson, A.Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitroJ. Pharmacol. Exp. Ther.230(1)94-102(1984) 2.Appl, H., Holzammer, T., Dove, S., et al.Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychoticsNaunyn-Schmiedebergs Arch. Pharmacol.385(2)145-170(2012) 3.Gross, G., Xin, X., and Gastpar, M.Trimipramine: Pharmacological reevaluation and comparison with clozapineNeuropharmacology30(11)1159-1166(1991) 4.Delini-Stula, A., Radeke, E., and van Riezen, H.Enhanced functional responsiveness of the dopaminergic system-the mechanism of anti-immobility effects of antidepressants in the behavioural despair test in the ratNeuropharmacology27(9)943-947(1988)