Desipramine is primarily used for the treatment of depression.[7] It may also be useful to treat symptoms ofattention-deficit hyperactivity disorder (ADHD).[8] Evidence of benefit is only in the short term, and with concerns of side effects its overall usefulness is not clear.[9] Desipramine at very low doses is also used to help reduce the pain associated withfunctional dyspepsia.[10] It has also been tried, albeit with little evidence of effectiveness, in the treatment ofcocaine dependence.[11] Evidence for usefulness inneuropathic pain is also poor.[12]
Desipramine is particularly toxic in cases of overdose, compared to other antidepressants.[14] 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 selectivenorepinephrine reuptake inhibitor (NRI), which is thought to enhancenoradrenergicneurotransmission.[33][34] Based on one study, it has the highest affinity for thenorepinephrine transporter (NET) of any other TCA,[16] and is said to be the most noradrenergic[35] and the most selective for the NET of the TCAs.[33] The observed effectiveness of desipramine in the treatment of ADHD was the basis for the development of the selective NRIatomoxetine and its use in ADHD.[33]
Desipramine has the weakestantihistamine andanticholinergic effects of the TCAs.[36][35][37] It tends to be slightlyactivating/stimulating rather thansedating, unlike most others TCAs.[35] Whereas other TCAs are useful for treatinginsomnia, desipramine can cause insomnia as a side effect due to its activating properties.[35] The drug is also not associated withweight gain, in contrast to many other TCAs.[35] Secondary amine TCAs like desipramine andnortriptyline have a lower risk oforthostatic hypotension than other TCAs,[38][39] although desipramine can still cause moderate orthostatic hypotension.[40]
Desipramine was developed byGeigy.[49] It first appeared in the literature in 1959 and was patented in 1962.[49] The drug was first introduced for the treatment of depression in 1963 or 1964.[49][50]
Desipramine is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name, whiledesipramine hydrochloride is itsUSANTooltip United States Adopted Name,USPTooltip United States Pharmacopeia,BANTooltip British Approved Name, andJANTooltip Japanese Accepted Name.[1][2][51][3] Its generic name inFrench and itsDCFTooltip Dénomination Commune Française aredésipramine, inSpanish andItalian and itsDCITTooltip Denominazione Comune Italiana aredesipramina, inGerman isdesipramin, and inLatin isdesipraminum.[2][3]
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):169–174.doi:10.2174/15748863113089990029.PMID23914752.
^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. Retrieved7 May 2022.
^abcdTatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters".European Journal of Pharmacology.340 (2–3):249–258.doi:10.1016/s0014-2999(97)01393-9.PMID9537821.
^abcdOwens MJ, Morgan WN, Plott SJ, Nemeroff CB (December 1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites".The Journal of Pharmacology and Experimental Therapeutics.283 (3):1305–1322.doi:10.1016/S0022-3565(24)37161-7.PMID9400006.
^abcdefgCusack B, Nelson A, Richelson E (May 1994). "Binding of antidepressants to human brain receptors: focus on newer generation compounds".Psychopharmacology.114 (4):559–565.doi:10.1007/bf02244985.PMID7855217.S2CID21236268.
^abWander TJ, Nelson A, Okazaki H, Richelson E (December 1986). "Antagonism by antidepressants of serotonin S1 and S2 receptors of normal human brain in vitro".European Journal of Pharmacology.132 (2–3):115–121.doi:10.1016/0014-2999(86)90596-0.PMID3816971.
^Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E, Hietala J (August 1996). "Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor".Psychopharmacology.126 (3):234–240.doi:10.1007/bf02246453.PMID8876023.S2CID24889381.
^abToll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, et al. (March 1998). "Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications".NIDA Research Monograph.178:440–466.PMID9686407.
^abcdeRichelson E, Nelson A (July 1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro".The Journal of Pharmacology and Experimental Therapeutics.230 (1):94–102.doi:10.1016/S0022-3565(25)21446-X.PMID6086881.
^Muth EA, Haskins JT, Moyer JA, Husbands GE, Nielsen ST, Sigg EB (December 1986). "Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative".Biochemical Pharmacology.35 (24):4493–4497.doi:10.1016/0006-2952(86)90769-0.PMID3790168.
^abcdAppl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (February 2012). "Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics".Naunyn-Schmiedeberg's Archives of Pharmacology.385 (2):145–170.doi:10.1007/s00210-011-0704-0.PMID22033803.S2CID14274150.
^abcdeStanton T, Bolden-Watson C, Cusack B, Richelson E (June 1993). "Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics".Biochemical Pharmacology.45 (11):2352–2354.doi:10.1016/0006-2952(93)90211-e.PMID8100134.
^abHindmarch I, Hashimoto K (April 2010). "Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered".Human Psychopharmacology.25 (3):193–200.doi:10.1002/hup.1106.PMID20373470.S2CID26491662.
^Leonard BE (October 1987). "A comparison of the pharmacological properties of the novel tricyclic antidepressant lofepramine with its major metabolite, desipramine: a review".International Clinical Psychopharmacology.2 (4):281–297.doi:10.1097/00004850-198710000-00001.PMID2891742.
^abcAndersen J, Kristensen AS, Bang-Andersen B, Strømgaard K (July 2009). "Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters".Chemical Communications (25):3677–3692.doi:10.1039/b903035m.PMID19557250.
