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

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
Biphasic effects of imipramine in experimental models of epilepsy.	1976 Jun	181243
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
Painful ejaculation associated with antidepressants in four patients.	1991 Nov	1744063
Lithium and calcium channel blockers: possible neurotoxicity.	1991 Sep 15	1932412
[Cardiac arrhythmia in amitriptyline poisoning in children].	2005 Apr-Jun	16607780
[Influence of chronic melipramine administration abolition on locomotion and defensive conditioned reflexes in passive and active avoidance in rats].	2005 Jan-Feb	15828425
Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha.	2005 Jul 29	15946935
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
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
[Treatment of anxiety syndrome. A systematic literature review. Summary and conclusions by the SBU].	2005 Nov 21-27	16408394
The role of serendipity in drug discovery.	2006	17117615
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
[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	16856516
Frequency of high-risk use of QT-prolonging medications.	2006 Jun	16178046
Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells.	2006 Mar 13	16324787
Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney.	2006 Nov	16928787
Mechanism of imipramine-induced seizures in amygdala-kindled rats.	2006 Nov	16914292
Recurrence of dilated cardiomyopathy after re-introduction of a tricyclic antidepressant.	2006 Oct	17100146
Polypharmacy and EPS in a child; a case report.	2007	17514191
Influence of antidepressants on hemostasis.	2007	17506225
Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.	2007 Aug 8	17617388
[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
In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies.	2007 Sep	17567588
Hereditary diffuse gastric cancer: association with lobular breast cancer.	2008	18046629
Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria.	2008 Dec	19043281
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
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action.	2008 Jul 28	18561912
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
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	18255130
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
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
Chronic administration of imipramine normalizes decreased sexual motivation and increased predisposition to catalepsy induced by propylthiouracil in rats.	2009 May	19340585
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.

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