IMIPRAMINE

First approved in 1959

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

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 8228
Norepinephrine transporter 190 Target ID: CHEMBL222 Sources: https://www.drugbank.ca/drugs/DB00458	Inhibitor 8228	12.0 nM [Ki]
Serotonin transporter 177 Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18983139	Inhibitor 8228	3.2 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 233 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/087846s028,087844s027,087845s027lbl.pdf	Primary		Approved 8360	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

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

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
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
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

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 n = 82 Health Status: unhealthy Condition: major depression \| melancholia Age Group: 18-70 years Population Size: 82 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 (starting) 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 Condition: depression 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 n = 82 Health Status: unhealthy Condition: major depression \| melancholia Age Group: 18-70 years Population Size: 82 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 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 n = 59 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: 42.6 ± 12.4 years Sex: M+F Population Size: 59 Sources: https://pubmed.ncbi.nlm.nih.gov/19653341
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf	unhealthy, < 24 years Health Status: unhealthy Condition: depression Age Group: < 24 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/017090s078lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709		substrate 1193	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT2 638 OCT3 149 MATE1 304 MATE2 261	CYP2C19 985 CYP1A2 1032 P-gp 1527 UGT2B10 127 UGT1A4 347 UGT1A3 422

Drug as perpetrator

Target	Modality	Activity
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 6 uM]
MATE2 261	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 182.9 uM]
MATE1 306	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 42 uM]
OCT3 149	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/10966924/	yes [Ki 42 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1032	substrate 3326 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
CYP2C19 985	substrate 3326 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
CYP2D6 1193	substrate 3326 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
CYP3A4 1709	substrate 3326 Sources: https://academic.oup.com/jat/article/38/6/368/2797982	yes
P-gp 1527	substrate 3326 Sources: https://academic.oup.com/ijnp/article/16/10/2259/653065	yes
UGT1A3 422	substrate 3326 Sources: https://sci-hub.do/10.1124/dmd.109.030981	yes
UGT1A4 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes
UGT2B10 127	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 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
Imipramine toxicity.	1975 Sep	1142523
Pediatric cardiovascular effects of imipramine and desipramine.	1991 Jan	2005043
Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.	1991 Nov	1786266
[Clinical-pharmacological case report: drug-induced inappropriate ADH secretion].	1992 Nov 17	1448636
The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation.	1999	10487422
The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria.	1999	10416826
Identification of a novel splice variant of heat shock cognate protein 70 after chronic antidepressant treatment in rat frontal cortex.	1999 Aug 2	10425221
Gabapentin therapy for cocaine cravings.	2000 Dec	11097986
Antidepressant drugs appear to enhance cocaine-induced toxicity.	2000 Feb	10743914
Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex.	2001 Apr 6	11257428
[Depression in the elderly. Medical treatment].	2001 Feb 24	11262813
Evaluation of the anti-inflammatory and anti-nociceptive effects of different antidepressants in the rat.	2003 Aug	12798668
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
[Hypnotherapy in the treatment of refractory nocturnal enuresis].	2004 Feb 19	14983195
Eugenol exhibits antidepressant-like activity in mice and induces expression of metallothionein-III in the hippocampus.	2004 Jun 18	15157811
[Effect of acute melipramine administration on motor activity and defensive conditioned reflexes of passive and active avoidance in rats].	2004 Nov-Dec	15658049
[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
Serotonin (5HT), fluoxetine, imipramine and dopamine target distinct 5HT receptor signaling to modulate Caenorhabditis elegans egg-laying behavior.	2005 Mar	15654117
UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation.	2005 May	15708967
[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
Polypharmacy and EPS in a child; a case report.	2007	17514191
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
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
Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression.	2009 May 28	19477151
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 `Wed Jul 05 22:46:31 UTC 2023` Edited by `admin` on `Wed Jul 05 22:46:31 UTC 2023`
Record UNII	OGG85SX4E4
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

IMIPRAMINE

Official 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

NSC-169866

Code

English

TRIMIPRAMINE MALEATE IMPURITY, IMIPRAMINE- [USP IMPURITY]

Common Name

English

Imipramine [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QN06AA02