Desipramine-d₄is intended for use as an internal standard for the quantification of desipramine by GC- or LC-MS. Desipramine is a tricyclic antidepressant and an active metabolite of imipramine .¹It inhibits the serotonin (5-HT) and norepinephrine transporters (K_is = 163 and 3.5 nM for human SERT and NET, respectively) and is an antagonist of the 5-HT receptor subtype 5-HT_2Aand the α₁-adrenergic receptor (α₁-AR), as well as histamine H₁and muscarinic acetylcholine receptors (mAChRs; K_is = 115, 23, 31, and 37 nM, respectively). Desipramine is selective for the 5-HT_2Areceptor over the 5-HT_1Areceptor (K_i= 2,272 nM) and for α₁-AR over α₂-AR (K_i= 1,379 nM). It also selectively inhibits G protein-activated inward rectifier potassium channel (GIRK), also known as K_ir3, currents inXenopusoocytes expressing human GIRK1 and GIRK2 or human GIRK1 and GIRK4 (IC₅₀s = 36.4 and 53.9 µM, respectively) over K_ir1.1 or K_ir2.1 currents inXenopusoocytes expressing the human channels (IC₅₀s = >100 µM for both).²Desipramine (3.2 mg/kg) decreases immobility time in the forced swim test in mice.³It also decreases flinching, as well as paw biting and licking, in the second phase of the formalin test in rats.⁴Formulations containing desipramine have been used in the treatment of depression.

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