IMIPRAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H24N2
Molecular Weight	280.4073
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CCCN1C2=CC=CC=C2CCC3=CC=CC=C13

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

Molecular Formula	C19H24N2
Molecular Weight	280.4073
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB00458
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serum paraoxonase/arylesterase 1 31 Target ID: P27169 Gene ID: 5444.0 Gene Symbol: PON1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23001316	Inhibitor 8504
Norepinephrine transporter 197 Target ID: CHEMBL222 Sources: https://www.drugbank.ca/drugs/DB00458	Inhibitor 8504	12.0 nM [Ki]
Serotonin transporter 183 Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18983139	Inhibitor 8504	3.2 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 240 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/087846s028,087844s027,087845s027lbl.pdf	Primary		Approved 8583	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 1984

C_max

Value	Dose	Co-administered	Analyte	Population
24.5 ng/mL OTHER https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/S0009-9236%2897%2990062-X	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
107 μg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/2185906/	130 mg 1 times / day steady-state, oral dose: 130 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Desipramine	Desipramine	IMIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
427 ng × h/mL OTHER https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/S0009-9236%2897%2990062-X	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
21.1 h OTHER https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/S0009-9236%2897%2990062-X	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
12 h REVIEW https://pubmed.ncbi.nlm.nih.gov/2185906/	130 mg 1 times / day steady-state, oral dose: 130 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Desipramine	Desipramine	IMIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
22% REVIEW https://pubmed.ncbi.nlm.nih.gov/2185906/	130 mg 1 times / day steady-state, oral dose: 130 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Desipramine	Desipramine	IMIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/9023787	unhealthy, 18-70 years Health Status: unhealthy Age Group: 18-70 years Sources: https://pubmed.ncbi.nlm.nih.gov/9023787	Disc. AE: Nausea... AEs leading to discontinuation/dose reduction: Nausea (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/9023787
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341	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: https://pubmed.ncbi.nlm.nih.gov/19653341
75 mg/day 1 times / day steady, oral Recommended Dose: 75 mg/day, 1 times / day Route: oral Route: steady Dose: 75 mg/day, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf	unhealthy, < 24 years Health Status: unhealthy Age Group: < 24 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf	Disc. AE: Suicidal ideation... AEs leading to discontinuation/dose reduction: Suicidal ideation (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/9023787	unhealthy, 18-70 years Health Status: unhealthy Age Group: 18-70 years Sources: https://pubmed.ncbi.nlm.nih.gov/9023787
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://pubmed.ncbi.nlm.nih.gov/19653341	unhealthy, 42.6 ± 12.4 years Health Status: unhealthy Age Group: 42.6 ± 12.4 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
Suicidal ideation	grade 5 Disc. AE	75 mg/day 1 times / day steady, oral Recommended Dose: 75 mg/day, 1 times / day Route: oral Route: steady Dose: 75 mg/day, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf	unhealthy, < 24 years Health Status: unhealthy Age Group: < 24 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT2 779 OCT3 159 MATE1 415 MATE2 267	CYP2C19 1119 CYP1A2 1197 P-gp 2052 UGT2B10 131 UGT1A4 399 UGT1A3 470

Drug as perpetrator

Target	Modality	Activity
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 6 uM]
MATE2 267	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 182.9 uM]
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 42 uM]
OCT3 161	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10966924/	yes [Ki 42 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
CYP2C19 1119	substrate 4014 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
CYP2D6 1388	substrate 4014 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
CYP3A4 1946	substrate 4014 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
P-gp 2052	substrate 4014 Sources: https://academic.oup.com/ijnp/article/16/10/2259/653065	yes
UGT1A3 470	substrate 4014 Sources: https://sci-hub.do/10.1124/dmd.109.030981	yes
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes
UGT2B10 131	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571643/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:47499	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:47499
ChemicalBook	CB1727489	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1727489
MolPort	MolPort-001-783-692	https://www.molport.com/shop/molecule-link/MolPort-001-783-692
ZINC	ZINC000000020245	http://zinc15.docking.org/substances/ZINC000000020245

PubMed

Title	Date	PubMed
The antinicotinic effects of drugs with clinically useful sedative-antianxiety properties.	1975	1803
One-year follow-up of hyperactive boys treated with imipramine or methylphenidate.	1975 Mar	1090193
Imipramine-induced heart block. A longitudinal case study.	1975 Mar 31	1173081
Imipramine dosage in children: a comment on "imipramine and electrocardiographic abnormalities in hyperactive children".	1975 May	1119617
Letter: Imipramine-induced heart block.	1975 Oct 27	1174365
Imipramine toxicity.	1975 Sep	1142523
Imipramine-induced syndrome of inappropriate antidiuretic hormone secretion.	1991 Dec	1749990
Pediatric cardiovascular effects of imipramine and desipramine.	1991 Jan	2005043
Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.	1991 Nov	1786266
Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial.	1999 Oct	10628889
Antidepressant drugs appear to enhance cocaine-induced toxicity.	2000 Feb	10743914
Sudden death of a child treated with imipramine. Case study.	2000 Winter	11191693
The use of short-form quality of life questionnaires to measure the impact of imipramine on women with urge incontinence.	2001	11715997
Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex.	2001 Apr 6	11257428
Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2.	2001 Dec	11714871
Adverse pulmonary vascular effects of high dose tricyclic antidepressants: acute and chronic animal studies.	2002 Aug	12212966
Phenelzine treatment increases transcription factor AP-2 levels in rat brain.	2003 Aug 28	12943557
Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients.	2003 Feb 1	12586234
Serotonergic platelet markers of suicidal behavior--do they really exist?	2004 Apr	15023476
Effect of anxiolytic, antidepressant, and antipsychotic drugs on cocaine-induced seizures and mortality.	2004 Dec	15582832
Three year naturalistic outcome study of panic disorder patients treated with paroxetine.	2004 Jun 11	15191617
Eugenol exhibits antidepressant-like activity in mice and induces expression of metallothionein-III in the hippocampus.	2004 Jun 18	15157811
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.	2004 Nov	15286053
[Influence of chronic melipramine administration abolition on locomotion and defensive conditioned reflexes in passive and active avoidance in rats].	2005 Jan-Feb	15828425
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Organophosphorothionate pesticides inhibit the bioactivation of imipramine by human hepatic cytochrome P450s.	2005 Jun 15	15922009
QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine.	2005 Mar	15687478
Exacerbation of harmaline-induced tremor by imipramine.	2005 May	15894058
UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation.	2005 May	15708967
Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.	2006 Feb	16637596
[Lack of antidepresant-like activity of some ligands of polyamine binding sites of NMDA receptors in models of depression].	2006 Jan-Feb	16579050
Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells.	2006 Mar 13	16324787
Mechanism of imipramine-induced seizures in amygdala-kindled rats.	2006 Nov	16914292
Influence of antidepressants on hemostasis.	2007	17506225
[Chemico-toxicological analysis of haloperidol in blood with high-performance liquid chromatography in combined poisoning].	2007 May-Jun	17598448
Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli.	2007 Nov 8	17988634
Hereditary diffuse gastric cancer: association with lobular breast cancer.	2008	18046629
Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants.	2008 Jan 14	17950272
Pharmacological separation of hEAG and hERG K+ channel function in the human mammary carcinoma cell line MCF-7.	2008 Jun	18497958
Gene expression profiling in rat liver treated with compounds inducing phospholipidosis.	2008 Jun 15	18355885
[Chronic imipramine treatment normalizes decreased sexual motivation and high predisposition to catalepsy induced by propylthiouracil in rat].	2008 Mar-Apr	18661784
Sub-chronic administration of rimonabant causes loss of antidepressive activity and decreases doublecortin immunoreactivity in the mouse hippocampus.	2009 Dec 25	19819298
Suppressive effect of imipramine on vincristine-induced mechanical allodynia in mice.	2009 Jul	19571391
Possible role of trazodone and imipramine in sleep deprivation-induced anxiety-like behavior and oxidative damage in mice.	2009 Jul-Aug	19798453
Behavioral changes in rats induced by a dipeptidyl peptidase IV inhibitor methionyl-2(S)-cyanopyrrolidine: experimental model of anxiety-depression disorder.	2009 Mar	19529845
A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel.	2009 Nov 1	19583963
Medicine and psychiatry in Western culture: Ancient Greek myths and modern prejudices.	2009 Oct 7	19811642
Imipramine enhances cell proliferation and decreases neurodegeneration in the hippocampus after transient global cerebral ischemia in rats.	2010 Feb 5	20036317
Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.	2010 Mar	19786086
Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment.	2010 May	19762159

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:51:42 GMT 2025` Edited by `admin` on `Mon Mar 31 17:51:42 GMT 2025`
Record UNII	OGG85SX4E4
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IMIPRAMINE

Official Name

English

NSC-169866

Preferred Name

English

MELIPRAMINE

Common Name

English

IMIPRAMINE [HSDB]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE IMPURITY B [EP IMPURITY]

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

TRIMIPRAMINE MALEATE IMPURITY D [EP IMPURITY]

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

5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 10,11-DIHYDRO-N,N-DIMETHYL-

Systematic Name

English

TRIMIPRAMINE MALEATE IMPURITY, IMIPRAMINE- [USP IMPURITY]

Common Name

English

Imipramine [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QN06AA02