Desipramine-d4 is 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 .1 It inhibits the serotonin (5-HT) and norepinephrine transporters (Kis = 163 and 3.5 nM for human SERT and NET, respectively) and is an antagonist of the 5-HT receptor subtype 5-HT2A and the α1-adrenergic receptor (α1-AR), as well as histamine H1 and muscarinic acetylcholine receptors (mAChRs; Kis = 115, 23, 31, and 37 nM, respectively). Desipramine is selective for the 5-HT2A receptor over the 5-HT1A receptor (Ki = 2,272 nM) and for α1-AR over α2-AR (Ki = 1,379 nM). It also selectively inhibits G protein-activated inward rectifier potassium channel (GIRK), also known as Kir3, currents in Xenopus oocytes expressing human GIRK1 and GIRK2 or human GIRK1 and GIRK4 (IC50s = 36.4 and 53.9 µM, respectively) over Kir1.1 or Kir2.1 currents in Xenopus oocytes expressing the human channels (IC50s = >100 µM for both).2 Desipramine (3.2 mg/kg) decreases immobility time in the forced swim test in mice.3 It also decreases flinching, as well as paw biting and licking, in the second phase of the formalin test in rats.4 Formulations containing desipramine have been used in the treatment of depression.
1.Owens, M.J., Neal, W., Plott, S.J., et al.Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolitesJ. Pharmacol. Exp. Ther.283(3)1305-1322(1997) 2.Kobayashi, T., Washiyama, K., and Ikeda, K.Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugsNeuropsychopharmacology29(10)1841-1851(2004) 3.Koek, W., Sandoval, T.L., and Daws, L.C.Effects of the antidepressants desipramine and fluvoxamine on latency to immobility and duration of immobility in the forced swim test in adult male C57BL/6J miceBehav. Pharmacol.29(5)453-456(2018) 4.Swaynok, J., Esser, M.J., and Reid, A.R.Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the ratPain82(2)149-158(1999)