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

Details

Stereochemistry ACHIRAL
Molecular Formula C19H24N2
Molecular Weight 280.408
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IMIPRAMINE

SMILES

CN(C)CCCN1c2ccccc2CCc3ccccc31

InChI

InChIKey=BCGWQEUPMDMJNV-UHFFFAOYSA-N
InChI=1S/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/087846s028,087844s027,087845s027lbl.pdf

Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. A tertiary amine, imipramine inhibits the reuptake of serotonin more so than most secondary amine tricyclics, meaning that it blocks the reuptake of neurotransmitters serotonin and noradrenaline almost equally. With chronic use, imipramine also down-regulates cerebral cortical β-adrenergic receptors and sensitizes post-synaptic sertonergic receptors, which also contributes to increased serotonergic transmission. It takes approximately 2 - 4 weeks for antidepressants effects to occur. The onset of action may be longer, up to 8 weeks, in some individuals. It is also effective in migraine prophylaxis, but not in abortion of acute migraine attack. Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, which is thought to contribute to relieving symptoms of depression. In addition to acutely inhibiting neurotransmitter re-uptake, imipramine causes down-regulation of cerebral cortical beta-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission. Used for relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older. May also be used to manage panic disorders, with or without agoraphobia, as a second line agent in ADHD, management of eating disorders, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, and for symptomatic treatment of postherpetic neuralgia.

CNS Activity

Curator's Comment:: CNS active and penetrant http://onlinelibrary.wiley.com/doi/10.1016/S0009-9236(03)90534-0/abstract;jsessionid=0501D49064CCA6E885143C367F1535B3.f02t02

Originator

Curator's Comment:: Roland Kuhn, Swiss psychiatrist, discovered the therapeutic affect of imipramine in depression in 1957 http://www.cinp.org/wp-content/uploads/2015/06/history1.pdf

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P27169
Gene ID: 5444.0
Gene Symbol: PON1
Target Organism: Homo sapiens (Human)
12.0 nM [Ki]
3.2 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Tofranil

Approved Use

Tofranil is used for: Treating depression. It is also used in some children to help reduce bedwetting. It may also be used for other conditions as determined by your doctor.

Launch Date

4.5394559E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
107 μg/L
130 mg 1 times / day steady-state, oral
dose: 130 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Desipramine
IMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
24.5 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

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

T1/2

ValueDoseCo-administeredAnalytePopulation
12 h
130 mg 1 times / day steady-state, oral
dose: 130 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Desipramine
IMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
21.1 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
22%
130 mg 1 times / day steady-state, oral
dose: 130 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Desipramine
IMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg/day 1 times / day steady, oral
Dose: 200 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 200 mg/day, 1 times / day
Sources:
unhealthy, 18-70 years
n = 82
Health Status: unhealthy
Condition: major depression | melancholia
Age Group: 18-70 years
Population Size: 82
Sources:
Disc. AE: Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (1 patient)
Sources:
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Disc. AE: Sleep disturbance, Urinary tract signs and symptoms NEC...
AEs leading to
discontinuation/dose reduction:
Sleep disturbance (3 patients)
Urinary tract signs and symptoms NEC (2 patients)
Palpitations (2 patients)
Anxiety (1 patient)
Dry mouth (1 patient)
Dizziness (3 patients)
Flushing (1 patient)
Constipation (1 patient)
Sources:
75 mg/day 1 times / day steady, oral (starting)
Recommended
Dose: 75 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 75 mg/day, 1 times / day
Sources:
unhealthy, < 24 years
Health Status: unhealthy
Condition: depression
Age Group: < 24 years
Sources:
Disc. AE: Suicidal ideation...
AEs leading to
discontinuation/dose reduction:
Suicidal ideation (grade 5)
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea 1 patient
Disc. AE
200 mg/day 1 times / day steady, oral
Dose: 200 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 200 mg/day, 1 times / day
Sources:
unhealthy, 18-70 years
n = 82
Health Status: unhealthy
Condition: major depression | melancholia
Age Group: 18-70 years
Population Size: 82
Sources:
Anxiety 1 patient
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Constipation 1 patient
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Dry mouth 1 patient
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Flushing 1 patient
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Palpitations 2 patients
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Urinary tract signs and symptoms NEC 2 patients
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Dizziness 3 patients
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Sleep disturbance 3 patients
Disc. AE
25 mg/day 1 times / day steady, oral
Dose: 25 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 25 mg/day, 1 times / day
Sources:
unhealthy, 42.6 ± 12.4 years
n = 59
Health Status: unhealthy
Condition: irritable bowel syndrome
Age Group: 42.6 ± 12.4 years
Sex: M+F
Population Size: 59
Sources:
Suicidal ideation grade 5
Disc. AE
75 mg/day 1 times / day steady, oral (starting)
Recommended
Dose: 75 mg/day, 1 times / day
Route: oral
Route: steady
Dose: 75 mg/day, 1 times / day
Sources:
unhealthy, < 24 years
Health Status: unhealthy
Condition: depression
Age Group: < 24 years
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Drug as perpetrator​

Drug as perpetrator​

Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
One-year follow-up of hyperactive boys treated with imipramine or methylphenidate.
1975 Mar
Cardiac arrhythmia and imipramine therapy.
1975 Mar 22
Imipramine-induced heart block. A longitudinal case study.
1975 Mar 31
Imipramine and electrocardiographic abnormalities in hyperactive children.
1975 May
Imipramine toxicity.
1975 Sep
Pediatric cardiovascular effects of imipramine and desipramine.
1991 Jan
Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.
1991 Nov
[Clinical-pharmacological case report: drug-induced inappropriate ADH secretion].
1992 Nov 17
Antidepressant drugs appear to enhance cocaine-induced toxicity.
2000 Feb
Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex.
2001 Apr 6
Moclobemide vs. imipramine in bipolar depression: a multicentre double-blind clinical trial.
2001 Aug
Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2.
2001 Dec
[Depression in the elderly. Medical treatment].
2001 Feb 24
Relative bioavailability of imipramine (Tofranil) coated tablets in healthy volunteers.
2001 Jun
Pharmacokinetics of imipramine in narcoleptic horses.
2001 May
Effect of fluoxetine and imipramine on the pharmacokinetics and tolerability of the antipsychotic quetiapine.
2002 Apr
Evaluation of the anti-inflammatory and anti-nociceptive effects of different antidepressants in the rat.
2003 Aug
N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases.
2003 Nov
Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.
2004
[Hypnotherapy in the treatment of refractory nocturnal enuresis].
2004 Feb 19
Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.
2004 Jul
Three year naturalistic outcome study of panic disorder patients treated with paroxetine.
2004 Jun 11
Eugenol exhibits antidepressant-like activity in mice and induces expression of metallothionein-III in the hippocampus.
2004 Jun 18
Long-term imipramine withdrawal induces a depressive-like behaviour in the forced swimming test.
2004 May 10
Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans.
2004 Nov
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.
2004 Nov
Mechanism of block of hEag1 K+ channels by imipramine and astemizole.
2004 Oct
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
2004 Oct
[Cardiac arrhythmia in amitriptyline poisoning in children].
2005 Apr-Jun
[Influence of chronic melipramine administration abolition on locomotion and defensive conditioned reflexes in passive and active avoidance in rats].
2005 Jan-Feb
Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha.
2005 Jul 29
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Organophosphorothionate pesticides inhibit the bioactivation of imipramine by human hepatic cytochrome P450s.
2005 Jun 15
[Treatment of anxiety syndrome. A systematic literature review. Summary and conclusions by the SBU].
2005 Nov 21-27
[Lack of antidepresant-like activity of some ligands of polyamine binding sites of NMDA receptors in models of depression].
2006 Jan-Feb
[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
Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells.
2006 Mar 13
Mechanism of imipramine-induced seizures in amygdala-kindled rats.
2006 Nov
Pharmacological separation of hEAG and hERG K+ channel function in the human mammary carcinoma cell line MCF-7.
2008 Jun
[Chronic imipramine treatment normalizes decreased sexual motivation and high predisposition to catalepsy induced by propylthiouracil in rat].
2008 Mar-Apr
Chronic coadministration of carbamazepine together with imipramine produces antidepressant-like effects in an ACTH-induced animal model of treatment-resistant depression: involvement of 5-HT(2A) receptors?
2008 May
Suppressive effect of imipramine on vincristine-induced mechanical allodynia in mice.
2009 Jul
Possible role of trazodone and imipramine in sleep deprivation-induced anxiety-like behavior and oxidative damage in mice.
2009 Jul-Aug
Behavioral changes in rats induced by a dipeptidyl peptidase IV inhibitor methionyl-2(S)-cyanopyrrolidine: experimental model of anxiety-depression disorder.
2009 Mar
Chronic administration of imipramine normalizes decreased sexual motivation and increased predisposition to catalepsy induced by propylthiouracil in rats.
2009 May
Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression.
2009 May 28
A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel.
2009 Nov 1
Medicine and psychiatry in Western culture: Ancient Greek myths and modern prejudices.
2009 Oct 7
Imipramine enhances cell proliferation and decreases neurodegeneration in the hippocampus after transient global cerebral ischemia in rats.
2010 Feb 5
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Depression Tablets: Initial dose: 100 mg orally per day Maintenance dose: 100 to 200 mg orally per day (If no response after 2 weeks, increase to 250 to 300 mg per day) Maximum dose: 300 mg orally per day
Route of Administration: Oral
The inhibition percentage of human PON1 for imipramine was 15.6% at 100 ug/L after incubation for 1 h). At 350 ug/L, the inhibition percentage for imipramine 19.2% after 1 h and 20.2% after 2 h.
Name Type Language
IMIPRAMINE
HSDB   INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
TRIMIPRAMINE MALEATE SPECIFIED IMPURITY D [EP]
Common Name English
MELIPRAMINE
Common Name English
IMIPRAMINE [HSDB]
Common Name English
SERMONIL
Common Name English
IMIPRAMINE [MI]
Common Name English
IMIPRAMINE [INN]
Common Name English
IMIPRAMINE [VANDF]
Common Name English
CRISTALIA
Common Name English
5-(3-(DIMETHYLAMINO)PROPYL)-10,11-DIHYDRO-5H-DIBENZ(B,F)AZEPINE
Systematic Name English
N-(.GAMMA.-DIMETHYLAMINOPROPYL)IMINODIBENZYL
Common Name English
BERKOMINE
Common Name English
ORG-2463
Code English
IMIPRAMINE [MART.]
Common Name English
ANTIDEPRIN
Common Name English
IMIPRAMINE [WHO-DD]
Common Name English
5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 10,11-DIHYDRO-N,N-DIMETHYL-
Systematic Name English
TRIMIPRAMINE MALEATE IMPURITY, IMIPRAMINE- [USP]
Common Name English
NSC-169866
Code English
Classification Tree Code System Code
WHO-VATC QN06AA02
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
LIVERTOX 502
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
WHO-ATC N06AA02
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
NCI_THESAURUS C94727
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
NDF-RT N0000175752
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
Code System Code Type Description
DRUG CENTRAL
1427
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
NCI_THESAURUS
C62039
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
INN
793
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
FDA UNII
OGG85SX4E4
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
MESH
D007099
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
EVMPD
SUB08152MIG
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-042-1
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
LACTMED
Imipramine
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
EPA CompTox
50-49-7
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
PUBCHEM
3696
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
ChEMBL
CHEMBL11
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
IUPHAR
357
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
MERCK INDEX
M6232
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY Merck Index
RXCUI
5691
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
IMIPRAMINE
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
DRUG BANK
DB00458
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
CAS
50-49-7
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY
HSDB
3100
Created by admin on Sat Jun 26 15:52:58 UTC 2021 , Edited by admin on Sat Jun 26 15:52:58 UTC 2021
PRIMARY