Desipramine

Source: Wikipedia, the free encyclopedia.
Not to be confused with depramine.
Desipramine
Skeletal formula of desipramine
Ball-and-stick model of the desipramine molecule
Clinical data
Trade namesNorpramin, Pertofrane, others
Other namesDesmethylimipramine; Norimipramine; EX-4355; G-35020; JB-8181; NSC-114901[1][2][3]
AHFS/Drugs.comMonograph
MedlinePlusa682387
Routes of
administration		Oral, intramuscular injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60–70%[6]
Protein binding91%[6]
MetabolismLiver (CYP2D6)[7]
Elimination half-life12–30 hours[6]
ExcretionUrine (70%), feces[6]
Identifiers
  • 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine
JSmol)
  • c1cc3c(cc1)CCc2c(cccc2)N3CCCNC
  • 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
  (verify)

Desipramine, sold under the brand name Norpramin among others, is a

overdose
.

Medical uses

Desipramine is primarily used for the treatment of depression.

attention-deficit hyperactivity disorder (ADHD).[9] Evidence of benefit 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 of effectiveness, in the treatment of cocaine dependence.[12] Evidence for usefulness in neuropathic pain is also poor.[13]

Side effects

Desipramine tends to be less

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]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter 17.6–163 Human [17][18]
NETTooltip Norepinephrine transporter 0.63–3.5 Human [17][18]
DATTooltip Dopamine transporter 3,190 Human [17]
5-HT1A ≥6,400 Human [19][20]
5-HT2A 115–350 Human [19][20]
5-HT2C 244–748 Rat [21][22]
5-HT3 ≥2,500 Rodent [22][23]
5-HT7 >1,000 Rat [24]
α1 23–130 Human [19][25][18]
α2 ≥1,379 Human [19][25][18]
β
 ≥1,700 Rat [26][27]
Cav2.2 410 Human [28]
D1
 5,460 Human [29]
D2
 3,400 Human [19][25]
H1 60–110 Human [19][25][30]
H2 1,550 Human [30]
H3 >100,000 Human [30]
H4 9,550 Human [30]
mAChTooltip Muscarinic acetylcholine receptor 66–198 Human [19][25]
  M1 110 Human [31]
  M2 540 Human [31]
  M3 210 Human [31]
  M4 160 Human [31]
  M5 143 Human [31]
σ1 1,990–4,000 Rodent [32][33]
σ2 ≥1,611 Rat [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

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

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

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

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. ^
    ISBN 978-1-4757-2085-3
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  2. ^
    ISBN 978-3-88763-075-1
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  3. ^ a b c d "Desipramine - Drugs.com". drugs.com.
  4. FDA
    . Retrieved 22 Oct 2023.
  5. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  6. ^
    ISBN 978-1-60913-345-0
    .
  7. S2CID 37529573
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  8. ^
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    .
  9. PMID 23914752
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  10. PMID 25238582
    .
  11. ^ "UpToDate". www.uptodate.com.
  12. PMID 22161371
    .
  13. PMID 25246131
    .
  14. ^ "Desipramine Hydrochloride". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. 13 December 2013. Retrieved 17 July 2014.
  15. PMID 19031375
    .
  16. ^ a b 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. Retrieved 7 May 2022.
  17. ^
    PMID 9537821
    .
  18. ^
    PMID 9400006
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  19. ^
    S2CID 21236268
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  20. ^
    PMID 3816971
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  21. S2CID 24889381
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  22. ^
    PMID 9686407
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  24. PMID 8394362
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  25. ^
    PMID 6086881
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  26. PMID 3790168
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  27. S2CID 19490821
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  28. PMID 16844100
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  29. PMID 17850785
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  30. ^
    S2CID 14274150
    .
  31. ^
    PMID 8100134
    .
  32. PMID 2877462
    .
  33. ^
    S2CID 26491662
    .
  34. ^
    ISBN 978-0-7817-6214-4
    .
  35. PMID 6384207
    .
  36. ^
    ISBN 978-0-323-41691-7
    .
  37. ISBN 978-0-8493-5680-3
    .
  38. ISBN 978-1-55009-248-6
    .
  39. ISBN 978-1-4615-5957-3
    .
  40. ISBN 978-1-58562-933-6
    .
  41. ISBN 978-1-4377-2190-4
    .
  42. PMID 2891742
    .
  43. ^
    ISBN 978-94-007-5805-6
    .
  44. ISBN 978-0-7817-6879-5
    .
  45. ISBN 978-0-471-95052-3
    .
  46. ISBN 978-3-527-64632-6
    .
  47. ISBN 978-1-56053-470-9
    .
  48. ISBN 978-0-19-162675-3
    .
  49. ^ Chambers M. "Desipramine dibudinate". ChemIDplus. U.S. National Library of Medicine.
  50. ^
    PMID 19557250
    .
  51. ISBN 978-0-7817-2845-4
    .
  52. ISBN 978-94-011-4439-1
    .

External links