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Details

Stereochemistry RACEMIC
Molecular Formula C20H26N2.C4H4O4
Molecular Weight 410.5069
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TRIMIPRAMINE MALEATE

SMILES

CC(CN(C)C)CN1c2ccccc2CCc3ccccc31.C(\[H])(=C(\[H])/C(=O)O)/C(=O)O

InChI

InChIKey=YDGHCKHAXOUQOS-BTJKTKAUSA-N
InChI=1S/C20H26N2.C4H4O4/c1-16(14-21(2)3)15-22-19-10-6-4-8-17(19)12-13-18-9-5-7-11-20(18)22;5-3(6)1-2-4(7)8/h4-11,16H,12-15H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula C20H26N2
Molecular Weight 294.4346
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula C4H4O4
Molecular Weight 116.0723
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Trimipramine is a tricyclic antidepressant similar to imipramine, but with more antihistaminic and sedative properties. It was sold under brand name surmontil for the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than other depressive states. In studies with neurotic outpatients, the drug appeared to be equivalent to amitriptyline in the less-depressed patients but somewhat less effective than amitriptyline in the more severely depressed patients. In hospitalized depressed patients, trimipramine and imipramine were equally effective in relieving depression. Trimipramine has been reported to differ from other typical tricyclic antidepressant drugs in several aspects, for instance it does not inhibit neuronal transmitter uptake and does not cause down-regulation of beta-adrenoceptors. Moreover, it may possess antipsychotic activity in schizophrenic patients. In addition, was found that it did not antagonize the inhibitory effect of noradrenaline and 5-hydroxytryptamine on the release of transmitter, mediated by presynaptic auto receptors. In radioligand binding studies, trimipramine showed fairly high affinities for some dopamine (DA), noradrenaline and 5-hydroxytryptamine (5-HT) receptor subtypes (5-HT2 receptors = alpha 1A/B-adrenoceptors greater than or equal to D2 receptors), intermediate affinities for D1 receptors, alpha 2B-adrenoceptors and 5-HT1C receptors but only low affinities for alpha 2A-adrenoceptors, 5-HT1A, 5-HT1D and 5-HT3 receptors. It may thus be classified as an atypical neuroleptic drug.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SURMONTIL

Approved Use

SURMONTIL is indicated for the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than other depressive states. In studies with neurotic outpatients, the drug appeared to be equivalent to amitriptyline in the less-depressed patients but somewhat less effective than amitriptyline in the more severely depressed patients. In hospitalized depressed patients, trimipramine and imipramine were equally effective in relieving depression.

Launch Date

2.97993601E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
92.1 ng/mL
75 mg single, oral
dose: 75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.13 μg × h/mL
75 mg single, oral
dose: 75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
31 h
75 mg single, oral
dose: 75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIMIPRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​

Drug as perpetrator​

Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
[Instead of benzodiazepines. An antidepressant as sleep aid].
2001 Jan 18
Seizure during combination of trimipramine and bupropion.
2001 Jun
Hydrophobia as a rare presentation of Cotard's syndrome: a case report.
2002 Aug
Connection between lithium and muscular incoordination.
2002 Feb
The effects of tricyclic antidepressants on breast cancer risk.
2002 Jan 7
[Delusional depression as differential dementia of the Alzheimer type diagnosis].
2002 May
Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.
2002 Sep
Effects of REM sleep awakenings and related wakening paradigms on the ultradian sleep cycle and the symptoms in depression.
2002 Sep-Oct
Optimised procedures for the reversed-phase liquid chromatographic analysis of formulations containing tricyclic antidepressants.
2003 Apr 24
Analysis of eighteen antidepressants, four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring.
2003 Aug 25
Antipsychotic efficacy of the antidepressant trimipramine: a randomized, double-blind comparison with the phenothiazine perazine.
2003 Mar-Apr
A comparative solid-phase extraction study for the simultaneous determination of fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiline, clomipramine, and trazodone in whole blood by capillary gas-liquid chromatography with nitrogen-phosphorus detection.
2003 Sep
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.
2004
Intrathecal tri-cyclic antidepressants produce spinal anesthesia.
2004 Nov
Risk of fetal exposure to tricyclic antidepressants.
2004 Oct
Intravenous administration of the neuropeptide galanin has fast antidepressant efficacy and affects the sleep EEG.
2004 Oct
Ghrelin plasma levels during psychopharmacological treatment.
2005
Antidepressants and their effect on sleep.
2005 Dec
Protonation of trimipramine salts of maleate, mesylate and hydrochloride observed by 1H, 13C and 15N NMR spectroscopy.
2005 Feb
Depression and sleep: pathophysiology and treatment.
2006
[Effects of antidepressants on sleep].
2006 Apr 30
[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
Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method.
2006 Oct 16
Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach.
2006 Oct 20
Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management.
2007
Antidepressants for the treatment of insomnia : a suitable approach?
2008
Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
2008 Apr 2
Determination of tricyclic antidepressants in human plasma using pipette tip solid-phase extraction and gas chromatography-mass spectrometry.
2008 Jul
The clinical-familial correlates and naturalistic outcome of panic-disorder-agoraphobia with and without lifetime bipolar II comorbidity.
2008 Nov 13
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.
2008 Nov 4
Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol--a double-blind multicenter trial.
2009 Apr
Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis.
2009 Apr 7
The effect of trimipramine on dream recall and dream emotions in depressive outpatients.
2009 May 30
Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.
2009 Oct
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine.
2010 May
Patents

Sample Use Guides

Outpatients and Office Patients: initially, 75 mg/day in divided doses, increased to 150 mg/day. Dosages over 200 mg/day are not recommended. Maintenance therapy is in the range of 50 to 150 mg/day. For convenient therapy and to facilitate patient compliance, the total dosage requirement may be given at bedtime. Hospitalized Patient: initially, 100 mg/day in divided doses. This may be increased gradually in a few days to 200 mg/day, depending upon individual response and tolerance. If improvement does not occur in 2 to 3 weeks, the dose may be increased to the maximum recommended dose of 250 to 300 mg/day. Adolescent and Geriatric Patients: initially, a dose of 50 mg/day is recommended, with gradual increments up to 100 mg/day, depending upon patient response and tolerance.
Route of Administration: Oral
It was investigated whether trimipramine and three of its metabolites interact with targets of other antidepressants, namely, the human monoamine transporters for noradrenaline (hNAT), serotonin (hSERT), and dopamine (hDAT), and with the human organic cation transporters (hOCT1, hOCT2, and hOCT3) which are expressed in the brain and are known to be involved in the uptake of monoamines. HEK293 cells heterologously expressing the abovementioned transporters were used to determine the inhibition of [(3)H]MPP(+) uptake by trimipramine and its main metabolites. At concentrations up to 30 μM, all transporters, except hOCT3, were inhibited by all examined substances. With IC(50) values between 2 and 10 μM, trimipramine inhibited hSERT, hNAT, hOCT1, and hOCT2, whereas clearly higher concentrations were needed for half-maximal inhibition of hDAT. Desmethyl-trimipramine showed about the same potencies as trimipramine, whereas 2-hydroxy-trimipramine was less potent at hNAT, hSERT, and hOCT1. Trimipramine-N-oxide preferentially inhibited hSERT.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:00:56 UTC 2021
Edited
by admin
on Fri Jun 25 21:00:56 UTC 2021
Record UNII
269K6498LD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIMIPRAMINE MALEATE
EP   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
TRIMIPRAMINE MALEATE [USAN]
Common Name English
5-(3-(DIMETHYLAMINO)-2-METHYLPROPYL)-10,11-DIHYDRO-5H-DIBENZ(B,F)AZEPINE MALEATE (1:1)
Systematic Name English
NSC-758386
Code English
TRIMIPRAMINE MALEATE [MI]
Common Name English
TRIMIPRAMINE MALEATE [EP MONOGRAPH]
Common Name English
TRIMIPRAMINE MALEATE [ORANGE BOOK]
Common Name English
TRIMIPRAMINE MALEATE [USP MONOGRAPH]
Common Name English
TRIMIPRAMINE MALEATE [JAN]
Common Name English
STANGYL
Brand Name English
TRIMIPRAMINE MALEATE [WHO-DD]
Common Name English
5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 10,11-DIHYDRO-N,N,.BETA.-TRIMETHYL-, (Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
SURMONTIL
Brand Name English
TRIMIPRAMINE MALEATE [MART.]
Common Name English
TRIMIPRAMINE MALEATE [USP-RS]
Common Name English
TRIMIPRAMINE MALEATE [VANDF]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
Code System Code Type Description
EPA CompTox
521-78-8
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
ECHA (EC/EINECS)
208-318-3
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
USP_CATALOG
1692709
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY USP-RS
CAS
20230-75-5
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
NON-SPECIFIC STOICHIOMETRY
MERCK INDEX
M11164
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY Merck Index
EVMPD
SUB04977MIG
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
RXCUI
71532
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY RxNorm
DRUG BANK
DBSALT000969
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL644
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
CAS
1217260-65-5
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
NON-SPECIFIC STEREOCHEMISTRY
CAS
521-78-8
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
NCI_THESAURUS
C47773
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
FDA UNII
269K6498LD
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
PUBCHEM
5282318
Created by admin on Fri Jun 25 21:00:56 UTC 2021 , Edited by admin on Fri Jun 25 21:00:56 UTC 2021
PRIMARY
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