Desipramine

Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression.<ref name="GG">Template:Cite book</ref> 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

Desipramine is primarily used for the treatment of depression.<ref name = GG/> It may also be useful to treat symptoms of attention-deficit hyperactivity disorder (ADHD).<ref>Template:Cite journal</ref> Evidence of benefit is only in the short term, and with concerns of side effects its overall usefulness is not clear.<ref>Template:Cite journal</ref> Desipramine at very low doses is also used to help reduce the pain associated with functional dyspepsia.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It has also been tried, albeit with little evidence of effectiveness, in the treatment of cocaine dependence.<ref>Template:Cite journal</ref> Evidence for usefulness in neuropathic pain is also poor.<ref name="pmid25246131">Template:Cite journal</ref>

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.<ref name = MD>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Overdose

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Desipramine is particularly toxic in cases of overdose, compared to other antidepressants.<ref>Template:Cite journal</ref> 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

citation

CitationClass=web }}</ref>
Site	Ki (nM)	Species	Ref
Template:Abbrlink	17.6–163	Human	<ref name="pmid9537821">Template:Cite journal</ref><ref name="pmid9400006">Template:Cite journal</ref>
Template:Abbrlink	0.63–3.5	Human	<ref name="pmid9537821" /><ref name="pmid9400006" />
Template:Abbrlink	3,190	Human	<ref name="pmid9537821" />
5-HT1A	≥6,400	Human	<ref name="pmid7855217" /><ref name="pmid3816971">Template:Cite journal</ref>
5-HT2A	115–350	Human	<ref name="pmid7855217" /><ref name="pmid3816971" />
5-HT2C	244–748	Rat	<ref name="pmid8876023">Template:Cite journal</ref><ref name="pmid9686407">Template:Cite journal</ref>
5-HT3	≥2,500	Rodent	<ref name="pmid9686407" /><ref name="pmid2533080">Template:Cite journal</ref>
5-HT7	>1,000	Rat	<ref name="pmid8394362">Template:Cite journal</ref>
α1	23–130	Human	<ref name="pmid7855217" /><ref name="pmid6086881" /><ref name="pmid9400006" />
α2	≥1,379	Human	<ref name="pmid7855217" /><ref name="pmid6086881" /><ref name="pmid9400006" />
β	≥1,700	Rat	<ref name="pmid3790168">Template:Cite journal</ref><ref name="pmid10379421">Template:Cite journal</ref>
Cav2.2	410	Human	<ref name="pmid16844100">Template:Cite journal</ref>
D1	5,460	Human	<ref name="pmid17850785">Template:Cite journal</ref>
D2	3,400	Human	<ref name="pmid7855217" /><ref name="pmid6086881" />
H1	60–110	Human	<ref name="pmid7855217">Template:Cite journal</ref><ref name="pmid6086881">Template:Cite journal</ref><ref name="pmid22033803">Template:Cite journal</ref>
H2	1,550	Human	<ref name="pmid22033803" />
H3	>100,000	Human	<ref name="pmid22033803" />
H4	9,550	Human	<ref name="pmid22033803" />
Template:Abbrlink	66–198	Human	<ref name="pmid7855217" /><ref name="pmid6086881" />
M1	110	Human	<ref name="pmid8100134">Template:Cite journal</ref>
M2	540	Human	<ref name="pmid8100134" />
M3	210	Human	<ref name="pmid8100134" />
M4	160	Human	<ref name="pmid8100134" />
M5	143	Human	<ref name="pmid8100134" />
σ1	1,990–4,000	Rodent	<ref name="pmid2877462">Template:Cite journal</ref><ref name="pmid20373470">Template:Cite journal</ref>
σ2	≥1,611	Rat	<ref name="PDSP" /><ref name="pmid20373470" />
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.<ref name="MartinVolkmar2007" /><ref name="pmid6384207">Template:Cite journal</ref> Based on one study, it has the highest affinity for the norepinephrine transporter (NET) of any other TCA,<ref name="pmid9537821" /> and is said to be the most noradrenergic<ref name="Curtin2016" /> and the most selective for the NET of the TCAs.<ref name="MartinVolkmar2007">Template:Cite book</ref> 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.<ref name="MartinVolkmar2007" />

Desipramine has the weakest antihistamine and anticholinergic effects of the TCAs.<ref name="GoldCarman1984">Template:Cite book</ref><ref name="Curtin2016">Template:Cite book</ref><ref name="BaylessDiehl2005">Template:Cite book</ref> It tends to be slightly activating/stimulating rather than sedating, unlike most others TCAs.<ref name="Curtin2016" /> Whereas other TCAs are useful for treating insomnia, desipramine can cause insomnia as a side effect due to its activating properties.<ref name="Curtin2016" /> The drug is also not associated with weight gain, in contrast to many other TCAs.<ref name="Curtin2016" /> Secondary amine TCAs like desipramine and nortriptyline have a lower risk of orthostatic hypotension than other TCAs,<ref name="Leigh2012">Template:Cite book</ref><ref name="HalesYudofsky2011">Template:Cite book</ref> although desipramine can still cause moderate orthostatic hypotension.<ref name="Rakel2007">Template:Cite book</ref>

Pharmacokinetics

Desipramine is the major metabolite of imipramine and lofepramine.<ref name="pmid2891742">Template:Cite journal</ref>

Chemistry

Desipramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure.<ref name="Ritsner2013">Template:Cite book</ref> Other dibenzazepine TCAs include imipramine (N-methyldesipramine), clomipramine, trimipramine, and lofepramine (N-(4-chlorobenzoylmethyl)desipramine).<ref name="Ritsner2013" /><ref name="LemkeWilliams2008">Template:Cite book</ref> Desipramine is a secondary amine TCA, with its N-methylated parent imipramine being a tertiary amine.<ref name="CutlerSramek1994">Template:Cite book</ref><ref name="AnzenbacherZanger2012">Template:Cite book</ref> Other secondary amine TCAs include nortriptyline and protriptyline.<ref name="Anthony2002">Template:Cite book</ref><ref name="CowenHarrison2012">Template:Cite book</ref> 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.<ref name="Elks2014" /> 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.<ref name="Elks2014" /><ref name="IndexNominum2000" /> 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.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="ChemIDplus">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

History

Desipramine was developed by Geigy.<ref name="pmid19557250">Template:Cite journal</ref> It first appeared in the literature in 1959 and was patented in 1962.<ref name="pmid19557250" /> The drug was first introduced for the treatment of depression in 1963 or 1964.<ref name="pmid19557250" /><ref name="Dart2004">Template:Cite book</ref>

Society and culture

Generic names

Desipramine is the generic name of the drug and its Template:Abbrlink and Template:Abbrlink, while desipramine hydrochloride is its Template:Abbrlink, Template:Abbrlink, Template:Abbrlink, and Template:Abbrlink.<ref name="Elks2014">Template:Cite book</ref><ref name="IndexNominum2000">Template:Cite book</ref><ref name="MortonHall2012">Template:Cite book</ref><ref name="Drugs.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Its generic name in French and its Template:Abbrlink are désipramine, in Spanish and Italian and its Template:Abbrlink are desipramina, in German is desipramin, and in Latin is desipraminum.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

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.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

External links

• Desipramine - MedlinePlus

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