Details
Stereochemistry | RACEMIC |
Molecular Formula | C20H26N2 |
Molecular Weight | 294.4338 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(CN(C)C)CN1C2=CC=CC=C2CCC3=CC=CC=C13
InChI
InChIKey=ZSCDBOWYZJWBIY-UHFFFAOYSA-N
InChI=1S/C20H26N2/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/h4-11,16H,12-15H2,1-3H3
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 |
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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 |
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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 Date1979 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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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 |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
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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 |
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PubMed
Title | Date | PubMed |
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Perazine for schizophrenia. | 2002 |
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Hydrophobia as a rare presentation of Cotard's syndrome: a case report. | 2002 Aug |
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Connection between lithium and muscular incoordination. | 2002 Feb |
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[Delusional depression as differential dementia of the Alzheimer type diagnosis]. | 2002 May |
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Is the nonREM-REM sleep cycle reset by forced awakenings from REM sleep? | 2002 Nov |
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Enantiomers' potential in psychopharmacology--a critical analysis with special emphasis on the antidepressant escitalopram. | 2002 Oct |
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Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study. | 2002 Sep |
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Effects of REM sleep awakenings and related wakening paradigms on the ultradian sleep cycle and the symptoms in depression. | 2002 Sep-Oct |
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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 |
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Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry. | 2003 Dec |
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Clinical outcome after trimipramine in patients with delusional depression - a pilot study. | 2003 Jan |
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Antipsychotic efficacy of the antidepressant trimipramine: a randomized, double-blind comparison with the phenothiazine perazine. | 2003 Mar-Apr |
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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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Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. | 2003 Oct |
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A comparative solid-phase extraction study for the simultaneous determination of fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiline, clomipramine, and trazodone in whole blood by capillary gas-liquid chromatography with nitrogen-phosphorus detection. | 2003 Sep |
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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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Risk of fetal exposure to tricyclic antidepressants. | 2004 Oct |
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The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants. | 2005 |
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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 |
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[Multiple fibromas in systemic mastocytosis]. | 2005 May |
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Depression and sleep: pathophysiology and treatment. | 2006 |
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[Treatment for irritable bowel syndrome--psychotropic drugs, antidepressants and so on]. | 2006 Aug |
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[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 |
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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 |
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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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Divalproex sodium in severe anaemia: a case report. | 2007 Jul 10 |
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Quantification of tricyclic antidepressants and monoamine oxidase inhibitors by high-performance liquid chromatography-tandem mass spectrometry in whole blood. | 2007 May |
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Receptor occupancy of mirtazapine determined by PET in healthy volunteers. | 2007 Nov |
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Antidepressant interactions with the NMDA NR1-1b subunit. | 2008 |
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Antidepressants for the treatment of insomnia : a suitable approach? | 2008 |
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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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Determination of tricyclic antidepressants in human plasma using pipette tip solid-phase extraction and gas chromatography-mass spectrometry. | 2008 Jul |
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Metabolism in adipose tissue in response to citalopram and trimipramine treatment--an in situ microdialysis study. | 2008 Jun |
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Frequency of different anti-depressants associated with suicides and drug deaths. | 2008 Mar |
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Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review. | 2008 Nov |
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Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies. | 2008 Nov 4 |
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Depression following thrombotic cardiovascular events in elderly medicare beneficiaries: risk of morbidity and mortality. | 2009 |
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Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol--a double-blind multicenter trial. | 2009 Apr |
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Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis. | 2009 Apr 7 |
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Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database. | 2009 Feb |
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Accuracy of Veterans Affairs databases for diagnoses of chronic diseases. | 2009 Oct |
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Drugs associated with more suicidal ideations are also associated with more suicide attempts. | 2009 Oct 2 |
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Persistent tinnitus induced by tricyclic antidepressants. | 2010 Aug |
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Interaction of the human plasma membrane monoamine transporter (hPMAT) with antidepressants and antipsychotics. | 2010 Jan |
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Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neurones in vitro. | 2010 Jan 1 |
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Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database. | 2010 Mar |
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Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. | 2010 May |
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.
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000175752
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WHO-ATC |
N06AA06
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WHO-VATC |
QN06AA06
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NCI_THESAURUS |
C94727
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LIVERTOX |
NBK547855
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SUB11314MIG
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10834
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C61990
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2758
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Trimipramine
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6S082C9NDT
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DB00726
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m11164
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739-71-9
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100000076927
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5584
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D014299
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TRIMIPRAMINE
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9738
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CHEMBL644
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ACTIVE MOIETY
METABOLITE (PARENT)
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SALT/SOLVATE (PARENT)