Desipramine is primarily used for the treatment of depression.[6] It may also be useful to treat symptoms of attention-deficit hyperactivity disorder (ADHD).[7] Evidence of benefit is only in the short term, and with concerns of side effects its overall usefulness is not clear.[8] Desipramine at very low doses is also used to help reduce the pain associated with functional dyspepsia.[9] It has also been tried, albeit with little evidence of effectiveness, in the treatment of cocaine dependence.[10] Evidence for usefulness in neuropathic pain is also poor.[11]
Desipramine is particularly toxic in cases of overdose, compared to other antidepressants.[13] Any overdose or suspected overdose of desipramine is considered to be a medical emergency and can result in death without prompt medical intervention.
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.
Desipramine is a very potent and relatively selective norepinephrine reuptake inhibitor (NRI), which is thought to enhance noradrenergicneurotransmission.[32][33] Based on one study, it has the highest affinity for the norepinephrine transporter (NET) of any other TCA,[15] and is said to be the most noradrenergic[34] and the most selective for the NET of the TCAs.[32] The observed effectiveness of desipramine in the treatment of ADHD was the basis for the development of the selective NRI atomoxetine and its use in ADHD.[32]
Desipramine has the weakest antihistamine and anticholinergic effects of the TCAs.[35][34][36] It tends to be slightly activating/stimulating rather than sedating, unlike most others TCAs.[34] Whereas other TCAs are useful for treating insomnia, desipramine can cause insomnia as a side effect due to its activating properties.[34] The drug is also not associated with weight gain, in contrast to many other TCAs.[34] Secondary amine TCAs like desipramine and nortriptyline have a lower risk of orthostatic hypotension than other TCAs,[37][38] although desipramine can still cause moderate orthostatic hypotension.[39]
Desipramine was developed by Geigy.[48] It first appeared in the literature in 1959 and was patented in 1962.[48] The drug was first introduced for the treatment of depression in 1963 or 1964.[48][49]
Desipramine is or has been marketed throughout the world under a variety of brand names, including Irene, Nebril, Norpramin, Pertofran, Pertofrane, Pertrofran, and Petylyl among others.[2][3]
^Ghanizadeh, A (July 2013). "A systematic review of the efficacy and safety of desipramine for treating ADHD". Current Drug Safety. 8 (3): 169–74. doi:10.2174/15748863113089990029. PMID23914752.
^Otasowie, J; Castells, X; Ehimare, UP; Smith, CH (Sep 19, 2014). "Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents". The Cochrane Database of Systematic Reviews. 9 (9): CD006997. doi:10.1002/14651858.CD006997.pub2. PMID25238582.
^ abRoth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 7 May 2022.
^ abcdTatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340 (2–3): 249–58. doi:10.1016/s0014-2999(97)01393-9. PMID9537821.
^ abcdOwens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites". J. Pharmacol. Exp. Ther. 283 (3): 1305–22. PMID9400006.
^ abcdefgCusack B, Nelson A, Richelson E (1994). "Binding of antidepressants to human brain receptors: focus on newer generation compounds". Psychopharmacology. 114 (4): 559–65. doi:10.1007/bf02244985. PMID7855217. S2CID21236268.
^ abWander TJ, Nelson A, Okazaki H, Richelson E (1986). "Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro". Eur. J. Pharmacol. 132 (2–3): 115–21. doi:10.1016/0014-2999(86)90596-0. PMID3816971.
^Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E, Hietala J (1996). "Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor". Psychopharmacology. 126 (3): 234–40. doi:10.1007/bf02246453. PMID8876023. S2CID24889381.
^ abToll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS (1998). "Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications". NIDA Res. Monogr. 178: 440–66. PMID9686407.
^ abcdeRichelson E, Nelson A (1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". J. Pharmacol. Exp. Ther. 230 (1): 94–102. PMID6086881.
^Sánchez C, Hyttel J (1999). "Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding". Cell. Mol. Neurobiol. 19 (4): 467–89. doi:10.1023/A:1006986824213. PMID10379421. S2CID19490821.
^Benjamin ER, Pruthi F, Olanrewaju S, Shan S, Hanway D, Liu X, Cerne R, Lavery D, Valenzano KJ, Woodward RM, Ilyin VI (September 2006). "Pharmacological characterization of recombinant N-type calcium channel (Cav2.2) mediated calcium mobilization using FLIPR". Biochem Pharmacol. 72 (6): 770–82. doi:10.1016/j.bcp.2006.06.003. PMID16844100.
^ abcdAppl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (2012). "Interactions of recombinant human histamine H1R, H2R, H3R, and H4R receptors with 34 antidepressants and antipsychotics". Naunyn Schmiedebergs Arch. Pharmacol. 385 (2): 145–70. doi:10.1007/s00210-011-0704-0. PMID22033803. S2CID14274150.
^ abcdeStanton T, Bolden-Watson C, Cusack B, Richelson E (1993). "Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics". Biochem. Pharmacol. 45 (11): 2352–4. doi:10.1016/0006-2952(93)90211-e. PMID8100134.
^ abHindmarch I, Hashimoto K (2010). "Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered". Hum Psychopharmacol. 25 (3): 193–200. doi:10.1002/hup.1106. PMID20373470. S2CID26491662.
^Leonard BE (1987). "A comparison of the pharmacological properties of the novel tricyclic antidepressant lofepramine with its major metabolite, desipramine: a review". Int Clin Psychopharmacol. 2 (4): 281–97. doi:10.1097/00004850-198710000-00001. PMID2891742.
^ abcAndersen J, Kristensen AS, Bang-Andersen B, Strømgaard K (2009). "Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters". Chem. Commun. (25): 3677–92. doi:10.1039/b903035m. PMID19557250.