U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C18H22N2
Molecular Weight 266.3813
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DESIPRAMINE

SMILES

CNCCCN1c2ccccc2CCc3ccccc31

InChI

InChIKey=HCYAFALTSJYZDH-UHFFFAOYSA-N
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

HIDE SMILES / InChI
Desipramine is a tricyclic antidepressant that was approved by the FDA in 1964. It was derived from imipramine, which was the first tricyclic antidepressant to be manufactured. Desipramine is one of many tricyclic antidepressants, and this type of antidepressant gets its name due to its three-ring chemical structure. Desipramine, a secondary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is the active metabolite of imipramine, a tertiary amine TCA. The acute effects of desipramine include inhibition of noradrenaline re-uptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxy tryptamine, 5HT) re-uptake at the serotoninergic nerve endings in the central nervous system. Desipramine exhibits greater noradrenergic re-uptake inhibition compared to the tertiary amine TCA imipramine. In addition to inhibiting neurotransmitter re-uptake, desipramine down-regulates beta-adrenergic receptors in the cerebral cortex and sensitizes serotonergic receptors with chronic use. The overall effect is increased serotonergic transmission. Antidepressant effects are typically observed 2 - 4 weeks following the onset of therapy though some patients may require up to 8 weeks of therapy prior to symptom improvement. Patients experiencing more severe depressive episodes may respond quicker than those with mild depressive symptoms. Desipramine is marketed under the trade name Norpramin, indicated for the treatment of depression.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NORPRAMIN

Approved Use

Desipramine hydrochloride tablets are indicated for the treatment of depression.

Launch Date

-1.61395196E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
21.8 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
656 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DESIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
9.78%
DESIPRAMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy, 2 years
n = 1
Health Status: healthy
Age Group: 2 years
Sex: F
Population Size: 1
Sources:
Other AEs: Coma, Seizures...
Other AEs:
Coma (grade 5, 1 patient)
Seizures (grade 5, 1 patient)
Hypotension (grade 5, 1 patient)
Sources:
300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, children | adolescents | and young adults
Health Status: unhealthy
Condition: major depressive disorde
Age Group: children | adolescents | and young adults
Sources:
Other AEs: Suicidal ideation...
AEs

AEs

AESignificanceDosePopulation
Coma grade 5, 1 patient
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy, 2 years
n = 1
Health Status: healthy
Age Group: 2 years
Sex: F
Population Size: 1
Sources:
Hypotension grade 5, 1 patient
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy, 2 years
n = 1
Health Status: healthy
Age Group: 2 years
Sex: F
Population Size: 1
Sources:
Seizures grade 5, 1 patient
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy, 2 years
n = 1
Health Status: healthy
Age Group: 2 years
Sex: F
Population Size: 1
Sources:
Suicidal ideation
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, children | adolescents | and young adults
Health Status: unhealthy
Condition: major depressive disorde
Age Group: children | adolescents | and young adults
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
no (co-administration study)
Comment: Ketoconazole did not alter the pharmacokinetics of orally administered desipramine in healthy volunteers; Genetic deficiency in CYP2D6 activity results in a 85% lower oral clearance of desipramine, as shown by a single dose pharmacokinetic study in healthy volunteers
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Low dose tricyclic tachycardia.
1991 Jan
Regulation of serotonin type 2 (5-HT2) and beta-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment.
1991 Nov
Reversal of desipramine toxicity in rats using drug-specific antibody Fab' fragment: effects on hypotension and interaction with sodium bicarbonate.
1992 Mar
Trazodone induction of migraine headache through mCPP.
1992 May
Bupropion-induced carbohydrate craving and weight gain.
1992 Oct
Effect of tolcapone on the haemodynamic effects and tolerability of desipramine.
2000
Antidepressant drugs appear to enhance cocaine-induced toxicity.
2000 Feb
Microheterogeneity of myocardial blood flow.
2001 Nov
Utility of crossover designs in clinical trials: efficacy of desipramine vs. placebo in opioid-dependent cocaine abusers.
2002 Spring
Prediction of treatment outcome by baseline urine cocaine results and self-reported cocaine use for cocaine and opioid dependence.
2003
Comorbid major depressive disorder as a prognostic factor in cocaine-abusing buprenorphine-maintained patients treated with desipramine and contingency management.
2003 Aug
Ethnic differences in substance abuse treatment retention, compliance, and outcome from two clinical trials.
2004 Feb
Clinical implications of genetic polymorphism of CYP2D6 in Mexican Americans.
2004 Jun 1
Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder.
2005 Feb
Interferon-alpha-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression.
2005 Jun
Interaction of organic cations with a newly identified plasma membrane monoamine transporter.
2005 Nov
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test.
2005 Oct
Frequency of high-risk use of QT-prolonging medications.
2006 Jun
Reduction of high-affinity beta2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopy.
2007 May 1
A possible role for the endocannabinoid system in the neurobiology of depression.
2007 Nov 19
An anti-immobility effect of exogenous corticosterone in mice.
2008 Feb 2
A novel approach for predicting antidepressant-induced sexual dysfunction in rats.
2008 Jan
Photophysics and photochemistry of imipramine, desimipramine, and clomipramine in several solvents: a fluorescence, 266 nm laser flash, and theoretical study.
2008 Jan 10
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action.
2008 Jul 28
Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression.
2008 Jun
Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators.
2009 Dec 18
Behavioral sensitization to cocaine: cooperation between glucocorticoids and epinephrine.
2009 Jul
Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3.
2009 Mar
Patents

Sample Use Guides

Usual Adult Dose for Depression 100 to 200 mg orally per day Maximum dose: 300 mg orally per day Comments: -Dosage should be initiated at a lower level and increased according to tolerance and clinical response. -In severely ill patients, dosage may be further increased to 300 mg per day if needed. -Treatment of patients requiring as much as 300 mg should generally be initiated in hospitals. Usual Geriatric Dose for Depression 25 to 100 mg orally per day Maximum dose: 150 mg orally per day
Route of Administration: Oral
Neuronal uptake 1 inhibitor desipramine (100 nM) decreased NE in 60-min hypothermic ischemia in isolated perfused guinea pig hearts.
Name Type Language
DESIPRAMINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
10,11-DIHYDRO-5-(3-(METHYLAMINO)PROPYL)-5H-DIBENZ(B,F)AZEPINE
Systematic Name English
N-DESMETHYLIMIPRAMINE
Common Name English
5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 10,11-DIHYDRO-N-METHYL-
Systematic Name English
DESIPRAMINE [VANDF]
Common Name English
DESIPRAMINE [WHO-DD]
Common Name English
DESIPRAMINE [HSDB]
Common Name English
IMIPRAMINE, DEMETHYL-
Common Name English
MONODEMETHYLIMIPRAMINE
Common Name English
IMIPRAMINE HYDROCHLORIDE IMPURITY A [EP]
Common Name English
DESIPRAMINE [INN]
Common Name English
NORIMIPRAMINE
Common Name English
DESIPRAMINE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
NDF-RT N0000175752
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
LIVERTOX 283
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
WHO-ATC N06AA01
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
WHO-VATC QN06AA01
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
Code System Code Type Description
CAS
50-47-5
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
ChEMBL
CHEMBL72
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
EPA CompTox
50-47-5
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
PUBCHEM
2995
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
EVMPD
SUB06995MIG
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
INN
1500
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-040-0
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
HSDB
3052
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
DRUG CENTRAL
812
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
RXCUI
3247
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY RxNorm
DRUG BANK
DB01151
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
MERCK INDEX
M4191
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY Merck Index
IUPHAR
2399
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
WIKIPEDIA
DESIPRAMINE
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
MESH
D003891
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
NCI_THESAURUS
C61700
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
FDA UNII
TG537D343B
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY
LACTMED
Desipramine
Created by admin on Sat Jun 26 12:09:23 UTC 2021 , Edited by admin on Sat Jun 26 12:09:23 UTC 2021
PRIMARY