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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

Molecular Formula C20H26N2
Molecular Weight 294.4338
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
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

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
Interaction of psychotropic drugs with monoamine oxidase in rat brain.
2001 Aug
[Instead of benzodiazepines. An antidepressant as sleep aid].
2001 Jan 18
Seizure during combination of trimipramine and bupropion.
2001 Jun
Differential effects of trimipramine and fluoxetine on sleep in geriatric depression.
2001 Mar
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
Perazine for schizophrenia.
2002
Hydrophobia as a rare presentation of Cotard's syndrome: a case report.
2002 Aug
Connection between lithium and muscular incoordination.
2002 Feb
[Delusional depression as differential dementia of the Alzheimer type diagnosis].
2002 May
Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry.
2003 Dec
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
Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor.
2003 Nov
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
Sleep disturbances, psychiatric disorders, and psychotropic drugs.
2005
Contribution of sleep research to the development of new antidepressants.
2005
Protonation of trimipramine salts of maleate, mesylate and hydrochloride observed by 1H, 13C and 15N NMR spectroscopy.
2005 Feb
2,2'-Bipyridine as a new and sensitive spectrophotometric reagent for the determination of nanoamounts of certain dibenzazepine class of tricyclic antidepressant drugs.
2005 Jan
[Effects of antidepressants on sleep].
2006 Apr 30
Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade.
2006 Oct
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
Aplastic right coronary artery and left coronary artery with a separate origin of the circumflex branch in a 31-year-old woman.
2007 Dec 20
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
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
Metabolism in adipose tissue in response to citalopram and trimipramine treatment--an in situ microdialysis study.
2008 Jun
Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review.
2008 Nov
The clinical-familial correlates and naturalistic outcome of panic-disorder-agoraphobia with and without lifetime bipolar II comorbidity.
2008 Nov 13
Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol--a double-blind multicenter trial.
2009 Apr
Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database.
2009 Feb
Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells.
2009 Jun
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
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 Dec 15 16:17:38 GMT 2023
Edited
by admin
on Fri Dec 15 16:17:38 GMT 2023
Record UNII
Y62G268P6X
Record Status Validated (UNII)
Record Version
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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
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