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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
Optimised procedures for the reversed-phase liquid chromatographic analysis of formulations containing tricyclic antidepressants.
2003 Apr 24
Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry.
2003 Dec
Trimipramine pharmacokinetics after intravenous and oral administration in carriers of CYP2D6 genotypes predicting poor, extensive and ultrahigh activity.
2003 Dec
Trimipramine determination in pharmaceutical preparations with an automated multicommutated reversed-flow system.
2003 Dec 4
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
Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP.
2004 Mar
Intrathecal tri-cyclic antidepressants produce spinal anesthesia.
2004 Nov
Intravenous administration of the neuropeptide galanin has fast antidepressant efficacy and affects the sleep EEG.
2004 Oct
Sleep and psychiatry.
2005
The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants.
2005
Ghrelin plasma levels during psychopharmacological treatment.
2005
Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.
2005 Jan
[Multiple fibromas in systemic mastocytosis].
2005 May
Galactorrhea during treatment with trimipramine. A case report.
2005 Nov
Depression and sleep: pathophysiology and treatment.
2006
The involvement of endogenous opioid mechanisms in the antinociceptive effects induced by antidepressant drugs, desipramine and trimipramine.
2006 Apr
Perazine for schizophrenia.
2006 Apr 19
[Effects of antidepressants on sleep].
2006 Apr 30
[Treatment for irritable bowel syndrome--psychotropic drugs, antidepressants and so on].
2006 Aug
[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
Trimipramine for refractory panic attacks.
2006 Mar
Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade.
2006 Oct
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
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
Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management.
2007
Differential neurotoxicity of tricyclic antidepressants and novel derivatives in vitro in a dorsal root ganglion cell culture model.
2007 Aug
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
Heart rate variability reveals risk of arrhythmias after intoxication with antidepressants.
2007 Jan
Divalproex sodium in severe anaemia: a case report.
2007 Jul 10
Quantification of tricyclic antidepressants and monoamine oxidase inhibitors by high-performance liquid chromatography-tandem mass spectrometry in whole blood.
2007 May
Antidepressant interactions with the NMDA NR1-1b subunit.
2008
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
Metabolism in adipose tissue in response to citalopram and trimipramine treatment--an in situ microdialysis study.
2008 Jun
The clinical-familial correlates and naturalistic outcome of panic-disorder-agoraphobia with and without lifetime bipolar II comorbidity.
2008 Nov 13
Depression following thrombotic cardiovascular events in elderly medicare beneficiaries: risk of morbidity and mortality.
2009
The combined dexamethasone/CRH Test (DEX/CRH test) and prediction of acute treatment response in major depression.
2009
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
Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database.
2009 Feb
Imaging biological activity of a glioblastoma treated with an individual patient-tailored, experimental therapy regimen.
2009 Jul
Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells.
2009 Jun
Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue.
2009 May 20
The effect of trimipramine on dream recall and dream emotions in depressive outpatients.
2009 May 30
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
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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