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Details

Stereochemistry RACEMIC
Molecular Formula C20H26N2.C4H4O4
Molecular Weight 410.506
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TRIMIPRAMINE MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CC(CN(C)C)CN1C2=C(CCC3=C1C=CC=C3)C=CC=C2

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 C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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 ( + / - )

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
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
The use of antidepressant drugs in dermatology.
2001 Nov
Separation of basic drug enantiomers by capillary electrophoresis using ovoglycoprotein as a chiral selector: comparison of chiral resolution ability of ovoglycoprotein and completely deglycosylated ovoglycoprotein.
2001 Sep
The effects of tricyclic antidepressants on breast cancer risk.
2002 Jan 7
Is the nonREM-REM sleep cycle reset by forced awakenings from REM sleep?
2002 Nov
Enantiomers' potential in psychopharmacology--a critical analysis with special emphasis on the antidepressant escitalopram.
2002 Oct
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
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
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
Tricyclic antidepressants as long-acting local anesthetics.
2003 May
abcb1ab P-glycoprotein is involved in the uptake of citalopram and trimipramine into the brain of mice.
2003 May-Jun
Prescribing cyclic antidepressants for vitiligo patients: which agents are superior, which are not?
2003 Nov-Dec
Sleep disturbances, psychiatric disorders, and psychotropic drugs.
2005
Contribution of sleep research to the development of new antidepressants.
2005
Ghrelin plasma levels during psychopharmacological treatment.
2005
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
[Multiple fibromas in systemic mastocytosis].
2005 May
The involvement of endogenous opioid mechanisms in the antinociceptive effects induced by antidepressant drugs, desipramine and trimipramine.
2006 Apr
Use of antidepressant medications in relation to the incidence of breast cancer.
2006 Apr 10
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
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
Antidepressant therapy in tinnitus.
2007 Apr
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
Divalproex sodium in severe anaemia: a case report.
2007 Jul 10
Antidepressant interactions with the NMDA NR1-1b subunit.
2008
Antidepressants for the treatment of insomnia : a suitable approach?
2008
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
Metabolism in adipose tissue in response to citalopram and trimipramine treatment--an in situ microdialysis study.
2008 Jun
Frequency of different anti-depressants associated with suicides and drug deaths.
2008 Mar
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
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.
2008 Nov 4
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
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
Interaction of the human plasma membrane monoamine transporter (hPMAT) with antidepressants and antipsychotics.
2010 Jan
Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neurones in vitro.
2010 Jan 1
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 Dec 15 19:09:46 GMT 2023
Edited
by admin
on Fri Dec 15 19:09:46 GMT 2023
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
Trimipramine maleate [WHO-DD]
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
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 Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID2045315
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
ECHA (EC/EINECS)
208-318-3
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
RS_ITEM_NUM
1692709
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
CAS
20230-75-5
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
NON-SPECIFIC STOICHIOMETRY
DAILYMED
269K6498LD
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
MERCK INDEX
m11164
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY Merck Index
CHEBI
35030
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
EVMPD
SUB04977MIG
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
RXCUI
71532
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY RxNorm
DRUG BANK
DBSALT000969
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
ChEMBL
CHEMBL644
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
NSC
758386
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
CAS
1217260-65-5
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
NON-SPECIFIC STEREOCHEMISTRY
SMS_ID
100000084667
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
CAS
521-78-8
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
NCI_THESAURUS
C47773
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
FDA UNII
269K6498LD
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
PUBCHEM
5282318
Created by admin on Fri Dec 15 19:09:46 GMT 2023 , Edited by admin on Fri Dec 15 19:09:46 GMT 2023
PRIMARY
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