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Details

Stereochemistry RACEMIC
Molecular Formula C20H26N2.CH4O3S
Molecular Weight 390.54
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIMIPRAMINE MESYLATE

SMILES

CS(O)(=O)=O.CC(CN(C)C)CN1C2=C(CCC3=C1C=CC=C3)C=CC=C2

InChI

InChIKey=KPPOZKAGJSXVND-UHFFFAOYSA-N
InChI=1S/C20H26N2.CH4O3S/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;1-5(2,3)4/h4-11,16H,12-15H2,1-3H3;1H3,(H,2,3,4)

HIDE SMILES / InChI
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

1979
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
Seizures associated with therapeutic doses of venlafaxine and trimipramine.
2000 Dec
Polysomnographic effects of adjuvant ginkgo biloba therapy in patients with major depression medicated with trimipramine.
2001 Mar
[Chronic sleep disorders. Masked depression].
2001 Oct 18
Connection between lithium and muscular incoordination.
2002 Feb
Effects of the atypical antidepressant trimipramine on neuronal excitability and long-term potentiation in guinea pig hippocampal slices.
2002 Feb
Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.
2002 Sep
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
Clinical outcome after trimipramine in patients with delusional depression - a pilot study.
2003 Jan
Antipsychotic efficacy of the antidepressant trimipramine: a randomized, double-blind comparison with the phenothiazine perazine.
2003 Mar-Apr
[Hypotensive cardio-circulatory failure and metabolic acidosis after suicidal intoxication with trimipramine and quetiapine. Case report and background].
2004 Jan
Automated determination of ziprasidone by HPLC with column switching and spectrophotometric detection.
2005 Apr
Protonation of trimipramine salts of maleate, mesylate and hydrochloride observed by 1H, 13C and 15N NMR spectroscopy.
2005 Feb
Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.
2005 Jan
[Multiple fibromas in systemic mastocytosis].
2005 May
[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
An electrospray ionisation tandem mass spectrometric investigation of selected psychoactive pharmaceuticals and its application in drug and metabolite profiling by liquid chromatography/electrospray ionisation tandem mass spectrometry.
2007
Antidepressant therapy in tinnitus.
2007 Apr
Divalproex sodium in severe anaemia: a case report.
2007 Jul 10
Antidepressants for the treatment of insomnia : a suitable approach?
2008
Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
2008 Feb
Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain.
2008 Jan 24
Determination of tricyclic antidepressants in human plasma using pipette tip solid-phase extraction and gas chromatography-mass spectrometry.
2008 Jul
Frequency of different anti-depressants associated with suicides and drug deaths.
2008 Mar
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
Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database.
2009 Feb
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Interaction of the human plasma membrane monoamine transporter (hPMAT) with antidepressants and antipsychotics.
2010 Jan
Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database.
2010 Mar
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.
Name Type Language
TRIMIPRAMINE MESYLATE
Common Name English
Trimipramine mesilate [WHO-DD]
Common Name English
5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 10,11-DIHYDRO-N,N,.BETA.-TRIMETHYL-, METHANESULFONATE (1:1)
Systematic Name English
TRIMIPRAMINE MESILATE
WHO-DD  
Common Name English
Code System Code Type Description
CAS
25332-13-2
Created by admin on Fri Dec 15 16:17:38 GMT 2023 , Edited by admin on Fri Dec 15 16:17:38 GMT 2023
PRIMARY
PUBCHEM
3045275
Created by admin on Fri Dec 15 16:17:38 GMT 2023 , Edited by admin on Fri Dec 15 16:17:38 GMT 2023
PRIMARY
EVMPD
SUB04978MIG
Created by admin on Fri Dec 15 16:17:38 GMT 2023 , Edited by admin on Fri Dec 15 16:17:38 GMT 2023
PRIMARY
RXCUI
236189
Created by admin on Fri Dec 15 16:17:38 GMT 2023 , Edited by admin on Fri Dec 15 16:17:38 GMT 2023
PRIMARY RxNorm
SMS_ID
100000090583
Created by admin on Fri Dec 15 16:17:38 GMT 2023 , Edited by admin on Fri Dec 15 16:17:38 GMT 2023
PRIMARY
EPA CompTox
DTXSID40948174
Created by admin on Fri Dec 15 16:17:38 GMT 2023 , Edited by admin on Fri Dec 15 16:17:38 GMT 2023
PRIMARY
FDA UNII
Y62G268P6X
Created by admin on Fri Dec 15 16:17:38 GMT 2023 , Edited by admin on Fri Dec 15 16:17:38 GMT 2023
PRIMARY