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Details

Stereochemistry UNKNOWN
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

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
Effects of chronic antidepressant treatments on 5-HT and NA transporters in rat brain: an autoradiographic study.
2001 Jan
Differential effects of trimipramine and fluoxetine on sleep in geriatric depression.
2001 Mar
The use of antidepressant drugs in dermatology.
2001 Nov
[Chronic sleep disorders. Masked depression].
2001 Oct 18
Effects of the atypical antidepressant trimipramine on neuronal excitability and long-term potentiation in guinea pig hippocampal slices.
2002 Feb
Effects of REM sleep awakenings and related wakening paradigms on the ultradian sleep cycle and the symptoms in depression.
2002 Sep-Oct
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
Prescribing cyclic antidepressants for vitiligo patients: which agents are superior, which are not?
2003 Nov-Dec
[Hypotensive cardio-circulatory failure and metabolic acidosis after suicidal intoxication with trimipramine and quetiapine. Case report and background].
2004 Jan
Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP.
2004 Mar
Automated determination of ziprasidone by HPLC with column switching and spectrophotometric detection.
2005 Apr
Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.
2005 Jan
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
[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
Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management.
2007
Divalproex sodium in severe anaemia: a case report.
2007 Jul 10
Antidepressant interactions with the NMDA NR1-1b subunit.
2008
Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain.
2008 Jan 24
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
Imaging biological activity of a glioblastoma treated with an individual patient-tailored, experimental therapy regimen.
2009 Jul
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
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 Sat Dec 16 11:48:03 UTC 2023
Edited
by admin
on Sat Dec 16 11:48:03 UTC 2023
Record UNII
I412286V22
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIMIPRAMINE MALEATE, (+)-
Common Name English
5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 10,11-DIHYDRO-N,N,.BETA.-TRIMETHYL-, (+)-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
(+)-TRIMIPRAMINE MALEATE
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
Code System Code Type Description
FDA UNII
I412286V22
Created by admin on Sat Dec 16 11:48:03 UTC 2023 , Edited by admin on Sat Dec 16 11:48:03 UTC 2023
PRIMARY
CAS
138283-61-1
Created by admin on Sat Dec 16 11:48:03 UTC 2023 , Edited by admin on Sat Dec 16 11:48:03 UTC 2023
PRIMARY
PUBCHEM
5282318
Created by admin on Sat Dec 16 11:48:03 UTC 2023 , Edited by admin on Sat Dec 16 11:48:03 UTC 2023
PRIMARY
Related Record Type Details
RACEMATE -> ENANTIOMER