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

Details

Stereochemistry ACHIRAL
Molecular Formula C23H16O6.2C19H24N2
Molecular Weight 949.1863
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IMIPRAMINE PAMOATE

SMILES

c1ccc2c(c1)cc(c(c2Cc3c4ccccc4cc(c3O)C(=O)O)O)C(=O)O.CN(C)CCCN1c2ccccc2CCc3ccccc31.CN(C)CCCN1c2ccccc2CCc3ccccc31

InChI

InChIKey=BPQZYOJIXDMZSX-UHFFFAOYSA-N
InChI=1S/C23H16O6.2C19H24N2/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;2*1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h1-10,24-25H,11H2,(H,26,27)(H,28,29);2*3-6,8-11H,7,12-15H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C19H24N2
Molecular Weight 280.408
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C23H16O6
Molecular Weight 388.3704
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
The antinicotinic effects of drugs with clinically useful sedative-antianxiety properties.
1975
Biphasic effects of imipramine in experimental models of epilepsy.
1976 Jun
Pediatric cardiovascular effects of imipramine and desipramine.
1991 Jan
Painful ejaculation associated with antidepressants in four patients.
1991 Nov
Lithium and calcium channel blockers: possible neurotoxicity.
1991 Sep 15
Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.
2004
Effect of anxiolytic, antidepressant, and antipsychotic drugs on cocaine-induced seizures and mortality.
2004 Dec
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
[Effect of acute melipramine administration on motor activity and defensive conditioned reflexes of passive and active avoidance in rats].
2004 Nov-Dec
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
A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system.
2005 Feb
Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system.
2005 Feb 16
[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
QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine.
2005 Mar
Serotonin (5HT), fluoxetine, imipramine and dopamine target distinct 5HT receptor signaling to modulate Caenorhabditis elegans egg-laying behavior.
2005 Mar
Exacerbation of harmaline-induced tremor by imipramine.
2005 May
UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation.
2005 May
[Treatment of anxiety syndrome. A systematic literature review. Summary and conclusions by the SBU].
2005 Nov 21-27
Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.
2006 Feb
[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
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
Mechanism of imipramine-induced seizures in amygdala-kindled rats.
2006 Nov
Recurrence of dilated cardiomyopathy after re-introduction of a tricyclic antidepressant.
2006 Oct
Polypharmacy and EPS in a child; a case report.
2007
Influence of antidepressants on hemostasis.
2007
Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli.
2007 Nov 8
Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants.
2008 Jan 14
Pharmacological separation of hEAG and hERG K+ channel function in the human mammary carcinoma cell line MCF-7.
2008 Jun
Gene expression profiling in rat liver treated with compounds inducing phospholipidosis.
2008 Jun 15
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
Sub-chronic administration of rimonabant causes loss of antidepressive activity and decreases doublecortin immunoreactivity in the mouse hippocampus.
2009 Dec 25
Possible role of trazodone and imipramine in sleep deprivation-induced anxiety-like behavior and oxidative damage in mice.
2009 Jul-Aug
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
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
Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.
2010 Mar
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 15:30:48 UTC 2021
Edited
by admin
on Sat Jun 26 15:30:48 UTC 2021
Record UNII
MC34P30298
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IMIPRAMINE PAMOATE
MI   ORANGE BOOK   USP-RS   VANDF  
Common Name English
IMIPRAMINE EMBONATE [MART.]
Common Name English
IMIPRAMINE PAMOATE [VANDF]
Common Name English
IMIPRAMINE EMBONATE
MART.   WHO-DD  
Common Name English
IMIPRAMINE EMBONATE [WHO-DD]
Common Name English
IMIPRAMINE PAMOATE [USP MONOGRAPH]
Common Name English
4,4'-METHYLENEBIS(3-HYDROXY-2-NAPHTHOIC) ACID, COMPOUND WITH 10,11-DIHYDRO-N,N-DIMETHYL-5H-DIBENZ(B,F)AZEPINE-5-PROPYLAMINE (1:2)
Common Name English
TOFRANIL-PM
Brand Name English
2-NAPHTHALENECARBOXYLIC ACID, 4,4'-METHYLENEBIS(3-HYDROXY-, COMPD. WITH 10,11-DIHYDRO-N,N-2-NAPHTHALENECARBOXYLIC ACID, 4,4'-METHYLENEBIS(3-HYDROXY-, COMPD. WITH 10,11-DIHYDRO-N,N-DIMETHYL-5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE (1:2)
Common Name English
IMIPRAMINE PAMOATE [ORANGE BOOK]
Common Name English
IMIPRAMINE PAMOATE [MI]
Common Name English
IMIPRAMINE PAMOATE [USP-RS]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
Code System Code Type Description
WIKIPEDIA
Imipramine pamoate
Created by admin on Sat Jun 26 15:30:49 UTC 2021 , Edited by admin on Sat Jun 26 15:30:49 UTC 2021
PRIMARY
EPA CompTox
10075-24-8
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
EVMPD
SUB02643MIG
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
ECHA (EC/EINECS)
233-206-6
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
FDA UNII
MC34P30298
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL11
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
PUBCHEM
24904
Created by admin on Sat Jun 26 15:30:49 UTC 2021 , Edited by admin on Sat Jun 26 15:30:49 UTC 2021
PRIMARY
NCI_THESAURUS
C61788
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
CAS
10075-24-8
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
RXCUI
91118
Created by admin on Sat Jun 26 15:30:49 UTC 2021 , Edited by admin on Sat Jun 26 15:30:49 UTC 2021
PRIMARY RxNorm
DRUG BANK
DBSALT000100
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY
MERCK INDEX
M6232
Created by admin on Sat Jun 26 15:30:48 UTC 2021 , Edited by admin on Sat Jun 26 15:30:48 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1338481
Created by admin on Sat Jun 26 15:30:49 UTC 2021 , Edited by admin on Sat Jun 26 15:30:49 UTC 2021
PRIMARY USP-RS
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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