Desipramine

Not to be confused with depramine.
Desipramine
Skeletal formula of desipramine
Ball-and-stick model of the desipramine molecule
Names
Trade namesNorpramin, Pertofrane, others
Other namesDesmethylimipramine; Norimipramine; EX-4355; G-35020; JB-8181; NSC-114901[1][2][3]
IUPAC name
  • 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine
Clinical data
Drug classTricyclic antidepressant[4]
Main usesDepression, panic disorder, postherpetic neuralgia[5]
Side effectsDry mouth, constipation, blurry vision, low blood pressure with standing, sleepiness, weakness[5]
Pregnancy
category
  • US: N (Not classified yet)
    Routes of
    use    		By mouth, intramuscular injection
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa682387
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability60–70%[6]
    Protein binding91%[6]
    MetabolismLiver (CYP2D6)[7]
    Elimination half-life12–30 hours[6]
    ExcretionUrine (70%), feces[6]
    Chemical and physical data
    FormulaC18H22N2
    Molar mass266.388 g·mol−1
    3D model (JSmol)
    SMILES
    • c1cc3c(cc1)CCc2c(cccc2)N3CCCNC
    InChI
    • InChI=1S/C18H22N2/c1-19-13-6-14-20-17-9-4-2-7-15(17)11-12-16-8-3-5-10-18(16)20/h2-5,7-10,19H,6,11-14H2,1H3 checkY
    • Key:HCYAFALTSJYZDH-UHFFFAOYSA-N checkY

    Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used to treat depression, panic disorder, and postherpetic neuralgia.[5] While benefits may be seen within 5 days, up to 3 weeks may be required for full effects.[5]

    Common side effects include dry mouth, constipation, blurry vision, low blood pressure with standing, sleepiness, and weakness.[5] Other side effects may include suicide, mania, arrythmias, and seizures.[5] Safety in pregnancy is unclear.[5] How it works is unclear, but is believed to involve effects on serotonin and norepinephrine.[5]

    Desipramine was approved for medical use in the United States in 1964.[5] It is available as a generic medication.[4] In the United States 30 tablets of 100 mg costs about 25 USD as of 2021.[8] It has been widely used.[4]

    Medical uses

    Desipramine is primarily used for the treatment of depression.[9]

    Evidence of benefit in attention-deficit hyperactivity disorder (ADHD) is only in the short term, and with concerns of side effects its overall usefulness is not clear.[10] Desipramine at very low doses is also used to help reduce the pain associated with functional dyspepsia.[11] It has also been tried, albeit with little evidence, in the treatment of cocaine dependence.[12] Evidence for usefulness in neuropathic pain is also poor.[13]

    Dosage

    It is generally started at a dose of 75 to 150 mg per day though may be increased up to 300 mg per day.[5] The typical long term doses is 100 to 200 mg per day.[4]

    Side effects

    Desipramine tends to be less sedating than other TCAs and tends to produce fewer anticholinergic effects such as dry mouth, constipation, urinary retention, blurred vision, and cognitive or memory impairments.[14]

    Overdose

    Main article: Tricyclic antidepressant overdose

    Desipramine is particularly toxic in cases of overdose, compared to other antidepressants.[15] Any overdose or suspected overdose of desipramine is considered to be a medical emergency and can result in death without prompt medical intervention.

    Pharmacology

    Pharmacodynamics

    See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles
    Desipramine[16]
    SiteKi (nM)SpeciesRef
    SERT17.6–163Human[17][18]
    NET0.63–3.5Human[17][18]
    DAT3,190Human[17]
    5-HT1A≥6,400Human[19][20]
    5-HT2A115–350Human[19][20]
    5-HT2C244–748Rat[21][22]
    5-HT3≥2,500Rodent[22][23]
    5-HT7>1,000Rat[24]
    α123–130Human[19][25][18]
    α2≥1,379Human[19][25][18]
    β≥1,700Rat[26][27]
    Cav2.2410Human[28]
    D15,460Human[29]
    D23,400Human[19][25]
    H160–110Human[19][25][30]
    H21,550Human[30]
    H3>100,000Human[30]
    H49,550Human[30]
    mACh66–198Human[19][25]
      M1110Human[31]
      M2540Human[31]
      M3210Human[31]
      M4160Human[31]
      M5143Human[31]
    σ11,990–4,000Rodent[32][33]
    σ2≥1,611Rat[16][33]
    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 noradrenergic neurotransmission.[34][35] Based on one study, it has the highest affinity for the norepinephrine transporter (NET) of any other TCA,[17] and is said to be the most noradrenergic[36] and the most selective for the NET of the TCAs.[34] 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.[34]

    Desipramine has the weakest antihistamine and anticholinergic effects of the TCAs.[37][36][38] It tends to be slightly activating/stimulating rather than sedating, unlike most others TCAs.[36] Whereas other TCAs are useful for treating insomnia, desipramine can cause insomnia as a side effect due to its activating properties.[36] The drug is also not associated with weight gain, in contrast to many other TCAs.[36] Secondary amine TCAs like desipramine and nortriptyline have a lower risk of orthostatic hypotension than other TCAs,[39][40] although desipramine can still cause moderate orthostatic hypotension.[41]

    Pharmacokinetics

    Desipramine is the major metabolite of imipramine and lofepramine.[42]

    Chemistry

    Desipramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure.[43] Other dibenzazepine TCAs include imipramine (N-methyldesipramine), clomipramine, trimipramine, and lofepramine (N-(4-chlorobenzoylmethyl)desipramine).[43][44] Desipramine is a secondary amine TCA, with its N-methylated parent imipramine being a tertiary amine.[45][46] Other secondary amine TCAs include nortriptyline and protriptyline.[47][48] The chemical name of desipramine is 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine and its free base form has a chemical formula of C18H22N2 with a molecular weight of 266.381 g/mol.[1] The drug is used commercially mostly as the hydrochloride salt; the dibudinate salt is or has been used for intramuscular injection in Argentina (brand name Nebril) and the free base form is not used.[1][2] The CAS Registry Number of the free base is 50-47-5, of the hydrochloride is 58-28-6, and of the dibudinate is 62265-06-9.[1][2][49]

    History

    Desipramine was developed by Geigy.[50] It first appeared in the literature in 1959 and was patented in 1962.[50] The drug was first introduced for the treatment of depression in 1963 or 1964.[50][51]

    Society and culture

    Generic names

    Desipramine is the generic name of the drug and its INN and BAN, while desipramine hydrochloride is its USAN, USP, BAN, and JAN.[1][2][52][3] Its generic name in French and its DCF are désipramine, in Spanish and Italian and its DCIT are desipramina, in German is desipramin, and in Latin is desipraminum.[2][3]

    Brand names

    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]

    References

    1. 1 2 3 4 5 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 363–. ISBN 978-1-4757-2085-3.
    2. 1 2 3 4 5 6 Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 304–. ISBN 978-3-88763-075-1.
    3. 1 2 3 4 "Desipramine - Drugs.com". drugs.com. Archived from the original on 2018-08-30. Retrieved 2021-02-10.
    4. 1 2 3 4 "Desipramine". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 6 May 2021. Retrieved 23 December 2021.
    5. 1 2 3 4 5 6 7 8 9 10 "Desipramine Monograph for Professionals". Drugs.com. Archived from the original on 27 January 2021. Retrieved 23 December 2021.
    6. 1 2 3 4 Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 588–. ISBN 978-1-60913-345-0. Archived from the original on 16 December 2019. Retrieved 10 February 2021.
    7. ↑ Sallee, FR; Pollock, BG (May 1990). "Clinical pharmacokinetics of imipramine and desipramine". Clinical Pharmacokinetics. 18 (5): 346–64. doi:10.2165/00003088-199018050-00002. PMID 2185906. S2CID 37529573.
    8. ↑ "Desipramine Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 23 December 2021.
    9. ↑ Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
    10. ↑ 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. PMID 25238582.
    11. ↑ "UpToDate". www.uptodate.com. Archived from the original on 2021-04-13. Retrieved 2021-02-10.
    12. ↑ Pani, PP; Trogu, E; Vecchi, S; Amato, L (December 2011). "Antidepressants for cocaine dependence and problematic cocaine use". The Cochrane Database of Systematic Reviews (12): CD002950. doi:10.1002/14651858.CD002950.pub3. PMID 22161371.
    13. ↑ Hearn L, Moore RA, Derry S, Wiffen PJ, Phillips T (2014). Hearn L (ed.). "Desipramine for neuropathic pain in adults". Cochrane Database Syst Rev (9): CD011003. doi:10.1002/14651858.CD011003.pub2. PMC 6804291. PMID 25246131.
    14. ↑ "Desipramine Hydrochloride". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. 13 December 2013. Archived from the original on 28 August 2021. Retrieved 17 July 2014.
    15. ↑ White, N; Litovitz, T; Clancy, C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology. 4 (4): 238–50. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.
    16. 1 2 Roth, 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. Archived from the original on 28 August 2021. Retrieved 14 August 2017.
    17. 1 2 3 4 Tatsumi 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. PMID 9537821.
    18. 1 2 3 4 Owens 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. PMID 9400006.
    19. 1 2 3 4 5 6 7 Cusack 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. PMID 7855217. S2CID 21236268.
    20. 1 2 Wander 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. PMID 3816971.
    21. ↑ 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. PMID 8876023. S2CID 24889381.
    22. 1 2 Toll 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. PMID 9686407.
    23. ↑ Schmidt AW, Hurt SD, Peroutka SJ (1989). "'[3H]quipazine' degradation products label 5-HT uptake sites". Eur. J. Pharmacol. 171 (1): 141–3. doi:10.1016/0014-2999(89)90439-1. PMID 2533080.
    24. ↑ Shen Y, Monsma FJ, Metcalf MA, Jose PA, Hamblin MW, Sibley DR (1993). "Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype". J. Biol. Chem. 268 (24): 18200–4. doi:10.1016/S0021-9258(17)46830-X. PMID 8394362.
    25. 1 2 3 4 5 Richelson E, Nelson A (1984). "Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro". J. Pharmacol. Exp. Ther. 230 (1): 94–102. PMID 6086881.
    26. ↑ Muth EA, Haskins JT, Moyer JA, Husbands GE, Nielsen ST, Sigg EB (1986). "Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative". Biochem. Pharmacol. 35 (24): 4493–7. doi:10.1016/0006-2952(86)90769-0. PMID 3790168.
    27. ↑ 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. PMID 10379421. S2CID 19490821.
    28. ↑ 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. PMID 16844100.
    29. ↑ Deupree JD, Montgomery MD, Bylund DB (2007). "Pharmacological properties of the active metabolites of the antidepressants desipramine and citalopram". Eur. J. Pharmacol. 576 (1–3): 55–60. doi:10.1016/j.ejphar.2007.08.017. PMC 2231336. PMID 17850785.
    30. 1 2 3 4 Appl 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. PMID 22033803. S2CID 14274150.
    31. 1 2 3 4 5 Stanton 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. PMID 8100134.
    32. ↑ Weber E, Sonders M, Quarum M, McLean S, Pou S, Keana JF (1986). "1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs". Proc. Natl. Acad. Sci. U.S.A. 83 (22): 8784–8. Bibcode:1986PNAS...83.8784W. doi:10.1073/pnas.83.22.8784. PMC 387016. PMID 2877462.
    33. 1 2 Hindmarch 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. PMID 20373470. S2CID 26491662.
    34. 1 2 3 Andrés Martin; Fred R. Volkmar; Melvin Lewis (2007). Lewis's Child and Adolescent Psychiatry: A Comprehensive Textbook. Lippincott Williams & Wilkins. pp. 764–. ISBN 978-0-7817-6214-4.
    35. ↑ Janowsky DS, Byerley B (1984). "Desipramine: an overview". J Clin Psychiatry. 45 (10 Pt 2): 3–9. PMID 6384207.
    36. 1 2 3 4 5 Catherine Curtin (19 January 2016). Pain Management, An Issue of Hand Clinics, E-Book. Elsevier Health Sciences. pp. 55–. ISBN 978-0-323-41691-7.
    37. ↑ Mark S. Gold; John S. Carman; R. Bruce Lydiard (2 July 1984). Advances in Psychopharmacology. CRC Press. pp. 98–. ISBN 978-0-8493-5680-3.
    38. ↑ Theodore M. Bayless; Anna Diehl (2005). Advanced Therapy in Gastroenterology and Liver Disease. PMPH-USA. pp. 263–. ISBN 978-1-55009-248-6.
    39. ↑ Hoyle Leigh (6 December 2012). Biopsychosocial Approaches in Primary Care: State of the Art and Challenges for the 21st Century. Springer Science & Business Media. pp. 108–. ISBN 978-1-4615-5957-3.
    40. ↑ Robert E. Hales; Stuart C. Yudofsky; Glen O. Gabbard (2011). Essentials of Psychiatry. American Psychiatric Pub. pp. 468–. ISBN 978-1-58562-933-6.
    41. ↑ Robert E. Rakel (May 2007). Textbook of Family Medicine E-Book. Elsevier Health Sciences. pp. 313–. ISBN 978-1-4377-2190-4.
    42. ↑ 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. PMID 2891742.
    43. 1 2 Michael S Ritsner (15 February 2013). Polypharmacy in Psychiatry Practice, Volume I: Multiple Medication Use Strategies. Springer Science & Business Media. pp. 270–271. ISBN 978-94-007-5805-6. Archived from the original on 8 September 2017. Retrieved 10 February 2021.
    44. ↑ Thomas L. Lemke; David A. Williams (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 580–. ISBN 978-0-7817-6879-5. Archived from the original on 2020-08-03. Retrieved 2021-02-10.
    45. ↑ Neal R. Cutler; John J. Sramek; Prem K. Narang (20 September 1994). Pharmacodynamics and Drug Development: Perspectives in Clinical Pharmacology. John Wiley & Sons. pp. 160–. ISBN 978-0-471-95052-3. Archived from the original on 3 August 2020. Retrieved 10 February 2021.
    46. ↑ Pavel Anzenbacher; Ulrich M. Zanger (23 February 2012). Metabolism of Drugs and Other Xenobiotics. John Wiley & Sons. pp. 302–. ISBN 978-3-527-64632-6. Archived from the original on 8 September 2017. Retrieved 10 February 2021.
    47. ↑ Patricia K. Anthony (2002). Pharmacology Secrets. Elsevier Health Sciences. pp. 39–. ISBN 978-1-56053-470-9. Archived from the original on 2019-12-16. Retrieved 2021-02-10.
    48. ↑ Philip Cowen; Paul Harrison; Tom Burns (9 August 2012). Shorter Oxford Textbook of Psychiatry. OUP Oxford. pp. 532–. ISBN 978-0-19-162675-3. Archived from the original on 8 September 2017. Retrieved 10 February 2021.
    49. ↑ Chambers, Michael. "ChemIDplus - 62265-06-9 - AMLRZIZSGSCSHZ-UHFFFAOYSA-N - Desipramine dibudinate - Similar structures search, synonyms, formulas, resource links, and other chemical information". chem.nlm.nih.gov. Archived from the original on 2017-08-14. Retrieved 2021-02-10.
    50. 1 2 3 Andersen 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. PMID 19557250.
    51. ↑ Richard C. Dart (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 836–. ISBN 978-0-7817-2845-4.
    52. ↑ I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 94–. ISBN 978-94-011-4439-1.
    Identifiers:
    This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.