Desipramine

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Desipramine
Skeletal formula of desipramine
Ball-and-stick model of the desipramine molecule
Clinical data
Trade namesNorpramin, Pertofrane, others
SynonymsDesmethylimipramine; Norimipramine; EX-4355; G-35020; JB-8181; NSC-114901[1][2][3]
AHFS/Drugs.comMonograph
MedlinePlusa682387
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Oral, intramuscular injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60–70%[5]
Protein binding91%[5]
MetabolismLiver (CYP2D6)[4]
Elimination half-life12–30 hours[5]
ExcretionUrine (70%), feces[5]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.000.037 Edit this at Wikidata
Chemical and physical data
FormulaC18H22N2
Molar mass266.381 g/mol
3D model (JSmol)
  (verify)

Desipramine, sold under the brand name Norpramin and Pertofrane among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression.[6] It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose.

Medical uses[edit]

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]

Side effects[edit]

Desipramine tends to be less sedating than other TCAs and tends to produce fewer anticholinergic effects like dry mouth, constipation, urinary retention, blurred vision, and cognitive/memory impairment.[12]

Overdose[edit]

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.

Pharmacology[edit]

Pharmacodynamics[edit]

Desipramine[14]
Site Ki (nM) Species Ref
SERT 17.6–163 Human [15][16]
NET 0.63–3.5 Human [15][16]
DAT 3,190 Human [15]
5-HT1A ≥6,400 Human [17][18]
5-HT2A 115–350 Human [17][18]
5-HT2C 244–748 Rat [19][20]
5-HT3 ≥2,500 Rodent [20][21]
5-HT7 >1,000 Rat [22]
α1 23–130 Human [17][23][16]
α2 ≥1,379 Human [17][23][16]
β ≥1,700 Rat [24][25]
D1 5,460 Human [26]
D2 3,400 Human [17][23]
H1 60–110 Human [17][23][27]
H2 1,550 Human [27]
H3 >100,000 Human [27]
H4 9,550 Human [27]
mACh 66–198 Human [17][23]
  M1 110 Human [28]
  M2 540 Human [28]
  M3 210 Human [28]
  M4 160 Human [28]
  M5 143 Human [28]
σ1 1,990–4,000 Rodent [29][30]
σ2 ≥1,611 Rat [14][30]
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.[31][32] 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[33] and the most selective for the NET of the TCAs.[31] 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.[31]

Desipramine has the weakest antihistamine and anticholinergic effects of the TCAs.[34][33][35] It tends to be slightly activating/stimulating rather than sedating, unlike most others TCAs.[33] Whereas other TCAs are useful for treating insomnia, desipramine can cause insomnia as a side effect due to its activating properties.[33] The drug is also not associated with weight gain, in contrast to many other TCAs.[33] Secondary amine TCAs like desipramine and nortriptyline have a lower risk of orthostatic hypotension than other TCAs,[36][37] although desipramine can still cause moderate orthostatic hypotension.[38]

Pharmacokinetics[edit]

Desipramine is the major metabolite of imipramine and lofepramine.[39]

Chemistry[edit]

Desipramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure.[40] Other dibenzazepine TCAs include imipramine (N-methyldesipramine), clomipramine, trimipramine, and lofepramine (N-(4-chlorobenzoylmethyl)desipramine).[40][41] Desipramine is a secondary amine TCA, with its N-methylated parent imipramine being a tertiary amine.[42][43] Other secondary amine TCAs include nortriptyline and protriptyline.[44][45] 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][46]

History[edit]

Desipramine was developed by Geigy.[47] It first appeared in the literature in 1959 and was patented in 1962.[47] The drug was first introduced for the treatment of depression in 1963 or 1964.[47][48]

Society and culture[edit]

Generic names[edit]

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][49][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[edit]

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[edit]

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External links[edit]