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

Details

Stereochemistry ACHIRAL
Molecular Formula C18H22N2
Molecular Weight 266.3807
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DESIPRAMINE

SMILES

CNCCCN1C2=C(CCC3=C1C=CC=C3)C=CC=C2

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

Molecular Formula C18H22N2
Molecular Weight 266.3807
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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 desipramine treatment of cocaine-related panic attacks.
1991 Dec
Repeated administration of desmethylimipramine blocks the reserpine-induced increase in tyrosine hydroxylase mRNA in locus coeruleus neurons of the rat.
1991 Jul
Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions.
1991 May
Desipramine-induced oral-pharyngeal disturbances: stuttering and jaw myoclonus.
1992 Dec
Effect of IAP and chronic antidepressant administration on the 5HT1A receptor in rat cortical membranes.
1992 May
Trazodone induction of migraine headache through mCPP.
1992 May
Antidepressant drugs appear to enhance cocaine-induced toxicity.
2000 Feb
Microheterogeneity of myocardial blood flow.
2001 Nov
Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine.
2002 Aug
Effects of catecholamine uptake blockers in the caudate-putamen and subregions of the medial prefrontal cortex of the rat.
2002 May 17
Prediction of treatment outcome by baseline urine cocaine results and self-reported cocaine use for cocaine and opioid dependence.
2003
Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics.
2003 Feb 21
Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients.
2003 Jun 5
Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain.
2003 Oct 1
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.
2004 Apr 15
Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes.
2004 Jan 9
Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.
2004 May 25
Brugada syndrome precipitated by a tricyclic antidepressant.
2005 May
Selective cortical VGLUT1 increase as a marker for antidepressant activity.
2005 Nov
The effects of desmethylimipramine on cyclic AMP-stimulated gene transcription in a model cell system.
2005 Sep 1
Anti-inflammatory properties of desipramine and fluoxetine.
2007 May 3
A possible role for the endocannabinoid system in the neurobiology of depression.
2007 Nov 19
A novel approach for predicting antidepressant-induced sexual dysfunction in rats.
2008 Jan
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action.
2008 Jul 28
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.
2008 Nov 4
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
Antidepressants influence somatostatin levels and receptor pharmacology in brain.
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.
Substance Class Chemical
Created
by admin
on Wed Jul 05 22:47:22 UTC 2023
Edited
by admin
on Wed Jul 05 22:47:22 UTC 2023
Record UNII
TG537D343B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DESIPRAMINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
Desipramine [WHO-DD]
Common 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 [HSDB]
Common Name English
IMIPRAMINE, DEMETHYL-
Common Name English
MONODEMETHYLIMIPRAMINE
Common Name English
IMIPRAMINE HYDROCHLORIDE IMPURITY A [EP IMPURITY]
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 Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
NDF-RT N0000175752
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
LIVERTOX NBK548233
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
WHO-ATC N06AA01
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
WHO-VATC QN06AA01
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
Code System Code Type Description
CAS
50-47-5
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
ChEMBL
CHEMBL72
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
EPA CompTox
DTXSID6022896
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
SMS_ID
100000083169
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
PUBCHEM
2995
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
EVMPD
SUB06995MIG
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
INN
1500
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
CHEBI
47781
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-040-0
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
HSDB
3052
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
DRUG CENTRAL
812
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
RXCUI
3247
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY RxNorm
DRUG BANK
DB01151
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
MERCK INDEX
M4191
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY Merck Index
IUPHAR
2399
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
WIKIPEDIA
DESIPRAMINE
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
MESH
D003891
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
NCI_THESAURUS
C61700
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
FDA UNII
TG537D343B
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
DAILYMED
TG537D343B
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
LACTMED
Desipramine
Created by admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Metabolizing reaction by CYP2D6: Hydroxylation
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
Pharmacological action: Tricyclic antidepressant drug (TCA)
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> METABOLITE ACTIVE
Imipramine has activities at both the serotonin and norepeinephrine transporters with greater affinity for the serotonin transporter while desipramine and 2-hydroxydesipramine have greater affinities for the norepinephrine transporter (Owens et al., 1997).
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY