TRIMIPRAMINE MESYLATE

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 Search

SMILES

CS(O)(=O)=O.CC(CN(C)C)CN1C2=CC=CC=C2CCC3=CC=CC=C13

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	CH4O3S
Molecular Weight	96.106
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
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	( + / - )

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/016792s037lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/1663593

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1663593	Antagonist 2849
Serotonin 2 (5-HT2) receptor 90 Target ID: CHEMBL2095200 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1663593	Antagonist 2849
Adrenergic receptors; alpha-1 A & B 8 Target ID: CHEMBL2096676 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1663593	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/016792s037lbl.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
92.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14520122/	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

Value	Dose	Co-administered	Analyte	Population
2.13 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14520122/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
31 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14520122/	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

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Ca2+ channels 59 Nav1.5 116 P-gp 1741	UGT1A4 399 CYP2C19 1119

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/7718613/; https://pubmed.ncbi.nlm.nih.gov/12650738/	likely
Ca2+ channels 62	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/1630591/	yes [IC50 31 uM]

Drug as victim

Target	Modality	Activity
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/016792s037lbl.pdf; https://pubmed.ncbi.nlm.nih.gov/31094902/; https://pubmed.ncbi.nlm.nih.gov/14520122/ Page: 6.0	likely
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	yes [Km 258 uM]
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/14520122/	yes
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/14520122/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 119	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/12749958/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9738	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9738
ChemicalBook	CB4490399	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4490399

PubMed

Title	Date	PubMed
Seizures associated with therapeutic doses of venlafaxine and trimipramine.	2000 Dec	11144696
Seizure during combination of trimipramine and bupropion.	2001 Jun	11465529
The use of antidepressant drugs in dermatology.	2001 Nov	11843209
Perazine for schizophrenia.	2002	11869638
Hydrophobia as a rare presentation of Cotard's syndrome: a case report.	2002 Aug	12121215
The effects of tricyclic antidepressants on breast cancer risk.	2002 Jan 7	11857018
Is the nonREM-REM sleep cycle reset by forced awakenings from REM sleep?	2002 Nov	12419411
Trimipramine pharmacokinetics after intravenous and oral administration in carriers of CYP2D6 genotypes predicting poor, extensive and ultrahigh activity.	2003 Dec	14646691
Clinical outcome after trimipramine in patients with delusional depression - a pilot study.	2003 Jan	12649769
abcb1ab P-glycoprotein is involved in the uptake of citalopram and trimipramine into the brain of mice.	2003 May-Jun	12650738
Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor.	2003 Nov	14647397
Prescribing cyclic antidepressants for vitiligo patients: which agents are superior, which are not?	2003 Nov-Dec	14526142
Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.	2004	15554748
Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP.	2004 Mar	15052513
Sleep disturbances, psychiatric disorders, and psychotropic drugs.	2005	16416708
Sleep and psychiatry.	2005	16416705
Ghrelin plasma levels during psychopharmacological treatment.	2005	15942258
Automated determination of ziprasidone by HPLC with column switching and spectrophotometric detection.	2005 Apr	15795645
Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.	2005 Jan	15706460
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	15652369
[Multiple fibromas in systemic mastocytosis].	2005 May	16372804
Galactorrhea during treatment with trimipramine. A case report.	2005 Nov	16342006
Use of antidepressant medications in relation to the incidence of breast cancer.	2006 Apr 10	16523201
[Effects of antidepressants on sleep].	2006 Apr 30	16780185
A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry technique for monitoring antidepressants in human serum.	2006 Feb	16418706
Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade.	2006 Oct	16388933
Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method.	2006 Oct 16	16859851
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	17534857
Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management.	2007	17453872
Heart rate variability reveals risk of arrhythmias after intoxication with antidepressants.	2007 Jan	17109100
Quantification of tricyclic antidepressants and monoamine oxidase inhibitors by high-performance liquid chromatography-tandem mass spectrometry in whole blood.	2007 May	17555643
Receptor occupancy of mirtazapine determined by PET in healthy volunteers.	2007 Nov	17653532
Antidepressant interactions with the NMDA NR1-1b subunit.	2008	20107576
Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.	2008 Apr 2	18382661
Frequency of different anti-depressants associated with suicides and drug deaths.	2008 Mar	17618448
Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review.	2008 Nov	18165262
Depression following thrombotic cardiovascular events in elderly medicare beneficiaries: risk of morbidity and mortality.	2009	20069046
The combined dexamethasone/CRH Test (DEX/CRH test) and prediction of acute treatment response in major depression.	2009	19177168
Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol--a double-blind multicenter trial.	2009 Apr	19038406
Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue.	2009 May 20	19457229
Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.	2009 Oct	19755002
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009 Oct 2	19798416
Persistent tinnitus induced by tricyclic antidepressants.	2010 Aug	19825900
Interaction of the human plasma membrane monoamine transporter (hPMAT) with antidepressants and antipsychotics.	2010 Jan	20012264
Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neurones in vitro.	2010 Jan 1	20015293
Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis.	2010 Jun	19635928
Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database.	2010 Mar	20036167
Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine.	2010 May	20133892

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Mon Mar 31 18:24:16 GMT 2025` Edited by `admin` on `Mon Mar 31 18:24:16 GMT 2025`
Record UNII	Y62G268P6X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRIMIPRAMINE MESYLATE

Common Name

English

TRIMIPRAMINE MESILATE

Preferred 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

Code System Code Type Description

CAS

25332-13-2