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 949.1841
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IMIPRAMINE PAMOATE

SMILES

CN(C)CCCN1C2=CC=CC=C2CCC3=CC=CC=C13.CN(C)CCCN4C5=CC=CC=C5CCC6=CC=CC=C46.OC(=O)C7=CC8=CC=CC=C8C(CC9=C%10C=CC=CC%10=CC(C(O)=O)=C9O)=C7O

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 280.4073
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C23H16O6
Molecular Weight 388.3695
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

1984
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
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
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
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
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
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
Health Status: unhealthy
Age Group: 18-70 years
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
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
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
Health Status: unhealthy
Age Group: 18-70 years
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 42.6 ± 12.4 years
Sex: M+F
Sources:
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:
unhealthy, < 24 years
Health Status: unhealthy
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
Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment.
2010-05
Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.
2010-03
Imipramine enhances cell proliferation and decreases neurodegeneration in the hippocampus after transient global cerebral ischemia in rats.
2010-02-05
Sub-chronic administration of rimonabant causes loss of antidepressive activity and decreases doublecortin immunoreactivity in the mouse hippocampus.
2009-12-25
A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel.
2009-11-01
Medicine and psychiatry in Western culture: Ancient Greek myths and modern prejudices.
2009-10-07
Possible role of trazodone and imipramine in sleep deprivation-induced anxiety-like behavior and oxidative damage in mice.
2009-10-03
Suppressive effect of imipramine on vincristine-induced mechanical allodynia in mice.
2009-07
Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression.
2009-05-28
Chronic administration of imipramine normalizes decreased sexual motivation and increased predisposition to catalepsy induced by propylthiouracil in rats.
2009-05
Behavioral changes in rats induced by a dipeptidyl peptidase IV inhibitor methionyl-2(S)-cyanopyrrolidine: experimental model of anxiety-depression disorder.
2009-03
Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria.
2008-12
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.
2008-11-04
[Chronic imipramine treatment normalizes decreased sexual motivation and high predisposition to catalepsy induced by propylthiouracil in rat].
2008-07-30
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action.
2008-07-28
Gene expression profiling in rat liver treated with compounds inducing phospholipidosis.
2008-06-15
Pharmacological separation of hEAG and hERG K+ channel function in the human mammary carcinoma cell line MCF-7.
2008-06
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?
2008-05
Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants.
2008-01-14
Hereditary diffuse gastric cancer: association with lobular breast cancer.
2008
Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli.
2007-11-08
In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies.
2007-09
Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.
2007-08-08
[Chemico-toxicological analysis of haloperidol in blood with high-performance liquid chromatography in combined poisoning].
2007-06-30
Polypharmacy and EPS in a child; a case report.
2007
Influence of antidepressants on hemostasis.
2007
Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney.
2006-11
Mechanism of imipramine-induced seizures in amygdala-kindled rats.
2006-11
Recurrence of dilated cardiomyopathy after re-introduction of a tricyclic antidepressant.
2006-10
[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].
2006-06
Frequency of high-risk use of QT-prolonging medications.
2006-06
[Cardiac arrhythmia in amitriptyline poisoning in children].
2006-04-13
[Lack of antidepresant-like activity of some ligands of polyamine binding sites of NMDA receptors in models of depression].
2006-04-04
Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells.
2006-03-13
Induction of neuroserpin expression in rat frontal cortex after chronic antidepressant treatment and electroconvulsive treatment.
2006-02
[Treatment of anxiety syndrome. A systematic literature review. Summary and conclusions by the SBU].
2006-01-18
The role of serendipity in drug discovery.
2006
Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha.
2005-07-29
Organophosphorothionate pesticides inhibit the bioactivation of imipramine by human hepatic cytochrome P450s.
2005-06-15
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005-06
Exacerbation of harmaline-induced tremor by imipramine.
2005-05
UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation.
2005-05
[Influence of chronic melipramine administration abolition on locomotion and defensive conditioned reflexes in passive and active avoidance in rats].
2005-04-15
Imipramine-induced syndrome of inappropriate antidiuretic hormone secretion.
1991-12
Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.
1991-11
Painful ejaculation associated with antidepressants in four patients.
1991-11
Lithium and calcium channel blockers: possible neurotoxicity.
1991-09-15
Pediatric cardiovascular effects of imipramine and desipramine.
1991-01
Biphasic effects of imipramine in experimental models of epilepsy.
1976-06
The antinicotinic effects of drugs with clinically useful sedative-antianxiety properties.
1975
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 Mon Mar 31 17:48:47 GMT 2025
Edited
by admin
on Mon Mar 31 17:48:47 GMT 2025
Record UNII
MC34P30298
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IMIPRAMINE EMBONATE
MART.   WHO-DD  
Preferred Name English
IMIPRAMINE PAMOATE
MI   ORANGE BOOK   USP-RS   VANDF  
Common Name English
IMIPRAMINE EMBONATE [MART.]
Common Name English
IMIPRAMINE PAMOATE [VANDF]
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 embonate [WHO-DD]
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 Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
Code System Code Type Description
WIKIPEDIA
Imipramine pamoate
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
EPA CompTox
DTXSID80143484
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
EVMPD
SUB02643MIG
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
DAILYMED
MC34P30298
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
ECHA (EC/EINECS)
233-206-6
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
SMS_ID
100000091075
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
FDA UNII
MC34P30298
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
ChEMBL
CHEMBL11
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
RS_ITEM_NUM
1338481
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
PUBCHEM
24904
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
NCI_THESAURUS
C61788
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
CAS
10075-24-8
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
RXCUI
91118
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY RxNorm
DRUG BANK
DBSALT000100
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY
MERCK INDEX
m6232
Created by admin on Mon Mar 31 17:48:47 GMT 2025 , Edited by admin on Mon Mar 31 17:48:47 GMT 2025
PRIMARY Merck Index
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY