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
Desipramine-induced oral-pharyngeal disturbances: stuttering and jaw myoclonus.
1992 Dec
Control of depression with fluoxetine and antiseizure medication in a brain-injured patient.
1992 Feb
Oral contraceptives and panic disorder.
1992 May
Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.
1999 Sep
Antidepressant drugs appear to enhance cocaine-induced toxicity.
2000 Feb
National Patterns of Medication Treatment for Depression, 1987 to 2001.
2001 Dec
Microheterogeneity of myocardial blood flow.
2001 Nov
[Effect of local and systemic desipramine administration on extracellular noradrenaline in the myocardium of rats].
2002 Dec
Antidepressants reduce phosphoinositide-specific phospholipase C (PI-PLC) activity and the mRNA and protein expression of selective PLC beta 1 isozyme in rat brain.
2002 Dec
Acute treatment with the cyclic antidepressant desipramine, but not fluoxetine, increases membrane-associated G protein-coupled receptor kinases 2/3 in rat brain.
2002 Dec
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
Validation of a simple, ethologically relevant paradigm for assessing anxiety in mice.
2003 Sep 1
Ethnic differences in substance abuse treatment retention, compliance, and outcome from two clinical trials.
2004 Feb
Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes.
2004 Jan 9
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.
2004 Nov
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
2004 Oct
Interferon-alpha-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression.
2005 Jun
Brugada syndrome precipitated by a tricyclic antidepressant.
2005 May
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test.
2005 Oct
Enhanced neurally evoked responses and inhibition of norepinephrine reuptake in rat mesenteric arteries after spinal transection.
2006 Jan
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].
2006 Jun
Frequency of high-risk use of QT-prolonging medications.
2006 Jun
Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro.
2007 Apr
Reduced evoked fos expression in activity-related brain regions in animal models of behavioral depression.
2007 Aug 15
Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells.
2007 May
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
The role of the entorhinal cortex in extinction: influences of aging.
2008
Do desipramine [10,11-dihydro-5-[3-(methylamino) propyl]-5H-dibenz[b,f]azepine monohydrochloride] and fluoxetine [N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-propan-1-amine] ameliorate the extent of colonic damage induced by acetic acid in rats?
2008 Dec
The 5-hydroxytryptamine2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl-4-piperidinemethanol (M100907) attenuates impulsivity after both drug-induced disruption (dizocilpine) and enhancement (antidepressant drugs) of differential-reinforcement-of-low-rate 72-s behavior in the rat.
2008 Dec
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
Association of changes in norepinephrine and serotonin transporter expression with the long-term behavioral effects of antidepressant drugs.
2009 May
MPTP-induced neuroblast apoptosis in the subventricular zone is not regulated by dopamine or other monoamine transporters.
2009 Nov
Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients.
2009 Oct 22
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 Fri Dec 16 16:39:03 UTC 2022
Edited
by admin
on Fri Dec 16 16:39:03 UTC 2022
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 Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
NDF-RT N0000175752
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
LIVERTOX NBK548233
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
WHO-ATC N06AA01
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
WHO-VATC QN06AA01
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
Code System Code Type Description
CAS
50-47-5
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
ChEMBL
CHEMBL72
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
EPA CompTox
DTXSID6022896
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
PUBCHEM
2995
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
EVMPD
SUB06995MIG
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
INN
1500
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
CHEBI
47781
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
ECHA (EC/EINECS)
200-040-0
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
HSDB
3052
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
DRUG CENTRAL
812
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
RXCUI
3247
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY RxNorm
DRUG BANK
DB01151
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
MERCK INDEX
M4191
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY Merck Index
IUPHAR
2399
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
WIKIPEDIA
DESIPRAMINE
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
MESH
D003891
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
NCI_THESAURUS
C61700
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
FDA UNII
TG537D343B
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
DAILYMED
TG537D343B
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
LACTMED
Desipramine
Created by admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
Metabolizing reaction by CYP2D6: Hydroxylation
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
Pharmacological action: Tricyclic antidepressant drug (TCA)
BINDER->LIGAND
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