Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H22ClN5O.ClH |
Molecular Weight | 408.325 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.ClC1=CC=CC(=C1)N2CCN(CCCN3N=C4C=CC=CN4C3=O)CC2
InChI
InChIKey=OHHDIOKRWWOXMT-UHFFFAOYSA-N
InChI=1S/C19H22ClN5O.ClH/c20-16-5-3-6-17(15-16)23-13-11-22(12-14-23)8-4-10-25-19(26)24-9-2-1-7-18(24)21-25;/h1-3,5-7,9,15H,4,8,10-14H2;1H
DescriptionCurator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB00656 | https://www.drugs.com/trazodone.html | http://reference.medscape.com/drug/oleptro-trazodone-d-342965
Curator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB00656 | https://www.drugs.com/trazodone.html | http://reference.medscape.com/drug/oleptro-trazodone-d-342965
Trazodone (brand name Oleptro, Desyrel, etc) is a serotonin uptake inhibitor that is used as an antidepressive agent. Trazodone binds to the 5-HT2 receptor, it acts as a serotonin agonist at high doses and a serotonin antagonist at low doses. Like fluoxetine, trazodone's antidepressant activity likely results from blockage of serotonin reuptake by inhibiting serotonin reuptake pump at the presynaptic neuronal membrane. If used for long time periods, postsynaptic neuronal receptor binding sites may also be affected. The sedative effect of trazodone is likely the result of alpha-adrenergic blocking action and modest histamine blockade at the H1 receptor. It weakly blocks presynaptic alpha2-adrenergic receptors and strongly inhibits postsynaptic alpha1 receptors. Trazodone does not affect the reuptake of norepinephrine or dopamine within the CNS. Because of its lack of anticholinergic side effects, trazodone is especially useful in situations in which antimuscarinic effects are particularly problematic (e.g., in patients with benign prostatic hyperplasia, closed-angle glaucoma, or severe constipation). Trazodone's propensity to cause sedation is a dual-edged sword. For many patients, the relief from agitation, anxiety, and insomnia can be rapid; for other patients, including those individuals with considerable psychomotor retardation and feelings of low energy, therapeutic doses of trazodone may not be tolerable because of sedation. Trazodone elicits orthostatic hypotension in some patients, probably as a consequence of α1-adrenergic receptor blockade. Mania has been observed in association with trazodone treatment, including in patients with bipolar disorder, as well as in patients with previous diagnoses of major depression. Compared to the reversible MAOI antidepressant drug moclobemide, significantly more impairment of vigilance occurs with trazodone.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703 |
17.0 nM [IC50] | ||
Target ID: CHEMBL2096904 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703 |
|||
Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568799 |
223.87 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | DESYREL Approved UseTrazodone Hydrochloride Tablets USP are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of Trazodone Hydrochloride Tablets USP has been established in trials with the immediate release formulation of trazodone [see Clinical Studies (14) Launch Date1981 |
|||
Primary | DESYREL Approved UseTrazodone Hydrochloride Tablets USP are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of Trazodone Hydrochloride Tablets USP has been established in trials with the immediate release formulation of trazodone [see Clinical Studies (14) Launch Date1981 |
|||
Primary | DESYREL Approved UseTrazodone Hydrochloride Tablets USP are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of Trazodone Hydrochloride Tablets USP has been established in trials with the immediate release formulation of trazodone [see Clinical Studies (14) Launch Date1981 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.88 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1438031/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TRAZODONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
13.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1438031/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TRAZODONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1438031/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TRAZODONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5% |
unknown, oral |
TRAZODONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Disc. AE: Drowsiness, Hypertension... AEs leading to discontinuation/dose reduction: Drowsiness (1 patient) Sources: Hypertension (1 patient) Vomiting (1 patient) |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Disc. AE: Dry mouth, Upset stomach... AEs leading to discontinuation/dose reduction: Dry mouth (1 patient) Sources: Upset stomach (1 patient) Drowsiness (1 patient) |
6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: |
unknown, 37 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 Sources: |
Disc. AE: Seizures, Hyponatremia... AEs leading to discontinuation/dose reduction: Seizures (grade 5, 1 patient) Sources: Hyponatremia (grade 5, 1 patient) |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: |
unknown, 55 years n = 1 Health Status: unknown Age Group: 55 years Sex: F Population Size: 1 Sources: |
Disc. AE: Arrhythmia... AEs leading to discontinuation/dose reduction: Arrhythmia (1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Drowsiness | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Hypertension | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Vomiting | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Co-administed with:: methyltestosterone(200 mg) Sources: |
unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 Sources: |
Drowsiness | 1 patient Disc. AE |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Dry mouth | 1 patient Disc. AE |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Upset stomach | 1 patient Disc. AE |
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Co-administed with:: alprazolam(8 mg) Sources: |
unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 Sources: |
Hyponatremia | grade 5, 1 patient Disc. AE |
6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: |
unknown, 37 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 Sources: |
Seizures | grade 5, 1 patient Disc. AE |
6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: |
unknown, 37 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 Sources: |
Arrhythmia | 1 patient Disc. AE |
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: |
unknown, 55 years n = 1 Health Status: unknown Age Group: 55 years Sex: F Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 23 uM] | ||||
yes [IC50 43 uM] | ||||
yes [IC50 45 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/11452702/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | yes (co-administration study) Comment: [PMID:7482685]: CYP2D6-mediated metabolism of trazodone is inhibited by coadministration of thioridazine, which is an inhibitor of this isozyme. |
|||
yes | yes (co-administration study) Comment: [DESYREL® LABEL]: The concomitant use of DESYREL and strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of DESYREL alone. The concomitant use of DESYREL and strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of DESYREL alone. |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea. | 2001 |
|
Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective. | 2001 |
|
The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5-HT3 receptor antagonism. | 2001 Apr |
|
Acute trazodone and quipazine treatment attenuates apomorphine-induced aggressive behaviour in male rats without major impact on emotional behaviour or monoamine content post mortem. | 2001 Apr |
|
Misdiagnosis of myoclonus in antidepressant induced serotonin excess. | 2001 Dec |
|
Recommendations for the management of behavioral and psychological symptoms of dementia. | 2001 Feb |
|
Screening for detection of new antidepressants, neuroleptics, hypnotics, and their metabolites in urine by GC-MS developed using rat liver microsomes. | 2001 Feb |
|
Treatment of the agitation of late-life psychosis and Alzheimer's disease. | 2001 Jan |
|
Weight outcomes among antidepressant users in nursing facilities. | 2001 Jan |
|
Serotonin syndrome. A common but often unrecognized psychiatric condition. | 2001 Jan |
|
Survey on the usefulness of trazodone in patients with PTSD with insomnia or nightmares. | 2001 Jul |
|
Pharmacology of erectile function and dysfunction. | 2001 May |
|
Evaluation of the absorption, excretion and metabolism of [14C] etoperidone in man. | 2001 Nov |
|
A display of hypomania in a depressed male in response to fluvoxamine. | 2001 Oct |
|
Antidepressant drug prescribing in Italy, 2000: analysis of a general practice database. | 2001 Oct |
|
Spectrophotometric, spectrofluorimetric and LC determination of trazodone hydrochloride. | 2001 Sep |
|
Citalopram-induced priapism. | 2002 Apr |
|
Effects of trazodone and imipramine on the biological rhythm: an analysis of sleep EEG and body core temperature. | 2002 Aug |
|
Relationship between plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine, and its clinical effect in depressed patients. | 2002 Aug |
|
Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol. | 2002 Aug |
|
Alpha(1)-adrenoceptor antagonists. 4. Pharmacophore-based design, synthesis, and biological evaluation of new imidazo-, benzimidazo-, and indoloarylpiperazine derivatives. | 2002 Aug 15 |
|
Alterations in 5-HT(1A) receptors and adenylyl cyclase response by trazodone in regions of rat brain. | 2002 Aug 16 |
|
Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. | 2002 Feb |
|
[Progress in therapy of erectile dysfunction. New orally administered drugs]. | 2002 May |
|
[Depression in epilepsy: symptom or syndrome?]. | 2002 Nov-Dec |
|
Voluntary undertaking rule and duty to warn. | 2002 Oct 1 |
|
Sleep in posttraumatic stress disorder. | 2002 Sep |
|
Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone. | 2003 Apr |
|
Pharmacologic management by clinical pharmacists of behavioral and psychological symptoms of dementia in nursing home residents: results from a pilot study. | 2003 Feb |
|
Electroanalytical characteristics of piribedil and its differential pulse and square wave voltammetric determination in pharmaceuticals and human serum. | 2003 Mar 10 |
|
Unexplained transient hyperphosphatemia is more common in acute psychiatric disorders than in acute medical-surgical conditions. | 2003 Mar 25 |
|
Dissociative symptoms from combined treatment with sertraline and trazodone. | 2003 Spring |
Sample Use Guides
Starting dose: 150 mg once daily. May be increased by 75 mg per day
every three days. Maximum dose: 375 mg per day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703
The receptors affinity was estimated at Nova Screen Laboratories by the ability of the Trazodone to displace selective radioligands. The assays were carried out using the following: for 5HT2A – rat cortical membranes, [3H]ketanserin (1.0 nM) as radioligand and methysergide as reference compound; for alpha1 - rat cortical membranes, [3H]prazosin (0.5 nM) and prazosin; for 5HT-R - rat forebrain membranes, [3H]citalopram (0.7 nM) and imipramine. In the preliminary binding assay, the results are expressed as inhibition percentage compared to results without drug and represent the average of duplicate tubes at each tested concentration in a single experiment.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C265
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9655
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C47767
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82112
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DTXSID8044626
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DBSALT000344
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62935
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100000090309
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292811
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6E8ZO8LRNM
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CHEMBL621
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6E8ZO8LRNM
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m11010
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246-855-5
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SUB15596MIG
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1673500
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25332-39-2
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ACTIVE MOIETY
SUBSTANCE RECORD