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
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-
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1663593 |
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Target ID: CHEMBL2095200 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1663593 |
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Target ID: CHEMBL2096676 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1663593 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | SURMONTIL Approved UseSURMONTIL 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 Date2.97993601E11 |
Cmax
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 |
T1/2
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 |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | ||||
yes [IC50 31 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely | ||||
yes [Km 258 uM] | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Interaction of psychotropic drugs with monoamine oxidase in rat brain. | 2001 Aug |
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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 |
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Hydrophobia as a rare presentation of Cotard's syndrome: a case report. | 2002 Aug |
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Is the nonREM-REM sleep cycle reset by forced awakenings from REM sleep? | 2002 Nov |
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abcb1ab P-glycoprotein is involved in the uptake of citalopram and trimipramine into the brain of mice. | 2003 May-Jun |
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Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor. | 2003 Nov |
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[Hypotensive cardio-circulatory failure and metabolic acidosis after suicidal intoxication with trimipramine and quetiapine. Case report and background]. | 2004 Jan |
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Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. | 2004 Mar |
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Ghrelin plasma levels during psychopharmacological treatment. | 2005 |
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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 |
|
Depression and sleep: pathophysiology and treatment. | 2006 |
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Use of antidepressant medications in relation to the incidence of breast cancer. | 2006 Apr 10 |
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[Treatment for irritable bowel syndrome--psychotropic drugs, antidepressants and so on]. | 2006 Aug |
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Trimipramine for refractory panic attacks. | 2006 Mar |
|
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 |
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Antidepressant therapy in tinnitus. | 2007 Apr |
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Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. | 2008 Apr 2 |
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Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment. | 2008 Feb |
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Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain. | 2008 Jan 24 |
|
Frequency of different anti-depressants associated with suicides and drug deaths. | 2008 Mar |
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The combined dexamethasone/CRH Test (DEX/CRH test) and prediction of acute treatment response in major depression. | 2009 |
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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 |
|
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 |
|
Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis. | 2010 Jun |
|
Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database. | 2010 Mar |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21484238
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
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on
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Thu Jul 06 02:17:54 UTC 2023
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Thu Jul 06 02:17:54 UTC 2023
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Record UNII |
269K6498LD
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Validated (UNII)
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C94727
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DTXSID2045315
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208-318-3
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1692709
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20230-75-5
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269K6498LD
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M11164
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35030
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SUB04977MIG
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DBSALT000969
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CHEMBL644
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758386
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521-78-8
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C47773
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269K6498LD
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
EP
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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ENANTIOMER -> RACEMATE | |||
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ENANTIOMER -> RACEMATE | |||
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PARENT -> SALT/SOLVATE |
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
UNSPECIFIED
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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ACTIVE MOIETY |