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
One-year follow-up of hyperactive boys treated with imipramine or methylphenidate.
1975 Mar
Cardiac arrhythmia and imipramine therapy.
1975 Mar 22
Imipramine-induced heart block. A longitudinal case study.
1975 Mar 31
Imipramine toxicity.
1975 Sep
On the anticataleptic action of cyproheptadine.
1976 Aug
Pediatric cardiovascular effects of imipramine and desipramine.
1991 Jan
Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.
1991 Nov
Lithium and calcium channel blockers: possible neurotoxicity.
1991 Sep 15
[Clinical-pharmacological case report: drug-induced inappropriate ADH secretion].
1992 Nov 17
Ocular toxicology.
1994 Dec
The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation.
1999
The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria.
1999
Identification of a novel splice variant of heat shock cognate protein 70 after chronic antidepressant treatment in rat frontal cortex.
1999 Aug 2
Neutrophil beta(2)-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome.
1999 Dec 15
Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial.
1999 Oct
Gabapentin therapy for cocaine cravings.
2000 Dec
Antidepressant drugs appear to enhance cocaine-induced toxicity.
2000 Feb
Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.
2000 Jul 28
Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex.
2001 Apr 6
[Depression in the elderly. Medical treatment].
2001 Feb 24
Pharmacokinetics of imipramine in narcoleptic horses.
2001 May
[Evaluation of analgesic action of fluvoxamine compared with efficacy of imipramine and tramadol for treatment of sciatica--open trial].
2002
Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients.
2003 Feb 1
Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.
2004
Serotonergic platelet markers of suicidal behavior--do they really exist?
2004 Apr
[Hypnotherapy in the treatment of refractory nocturnal enuresis].
2004 Feb 19
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
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
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.
2004 Oct
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
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
[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
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
Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.
2007 Aug 8
[Chemico-toxicological analysis of haloperidol in blood with high-performance liquid chromatography in combined poisoning].
2007 May-Jun
In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies.
2007 Sep
Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants.
2008 Jan 14
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action.
2008 Jul 28
Pharmacological separation of hEAG and hERG K+ channel function in the human mammary carcinoma cell line MCF-7.
2008 Jun
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.
2008 Nov 4
Suppressive effect of imipramine on vincristine-induced mechanical allodynia in mice.
2009 Jul
A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel.
2009 Nov 1
Imipramine enhances cell proliferation and decreases neurodegeneration in the hippocampus after transient global cerebral ischemia in rats.
2010 Feb 5
Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment.
2010 May
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
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY