TRAZODONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H22ClN5O
Molecular Weight	371.864
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC(=CC=C1)N2CCN(CCCN3N=C4C=CC=CN4C3=O)CC2

InChI

InChIKey=PHLBKPHSAVXXEF-UHFFFAOYSA-N

InChI=1S/C19H22ClN5O/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

HIDE SMILES / InChI

Molecular Formula	C19H22ClN5O
Molecular Weight	371.864
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/18207s030lbl.pdf
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	Potency
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703	Agonist 2752	17.0 nM [IC50]
Serotonin (5-HT) receptor 34 Target ID: CHEMBL2096904 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703	Agonist 2752
Serotonin 1a (5-HT1a) receptor 177 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568799	Agonist 2752	223.87 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Major depressive disorder 179 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022411lbl.pdf	Primary	Approved 8583	DESYREL Approved Use Trazodone 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 Date 1981
Insomnia 111 Sources: https://clinicaltrials.gov/ct2/show/NCT01662297	Primary	Phase IV 63	DESYREL Approved Use Trazodone 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 Date 1981
Alzheimer’s disease 278 Sources: https://clinicaltrials.gov/ct2/show/NCT00000179	Primary	Phase III 665	DESYREL Approved Use Trazodone 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 Date 1981

C_max

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

T_1/2

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

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/018207s033lbl.pdf	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 Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years Health Status: unknown Age Group: 22 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	Disc. AE: Drowsiness, Hypertension... AEs leading to discontinuation/dose reduction: Drowsiness (1 patient) Hypertension (1 patient) Vomiting (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years Health Status: unknown Age Group: 25 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	Disc. AE: Dry mouth, Upset stomach... AEs leading to discontinuation/dose reduction: Dry mouth (1 patient) Upset stomach (1 patient) Drowsiness (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28816830/	unknown, 37 years Health Status: unknown Age Group: 37 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/28816830/	Disc. AE: Seizures, Hyponatremia... AEs leading to discontinuation/dose reduction: Seizures (grade 5, 1 patient) Hyponatremia (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/28816830/
2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31879415/	unknown, 55 years Health Status: unknown Age Group: 55 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/31879415/	Disc. AE: Arrhythmia... AEs leading to discontinuation/dose reduction: Arrhythmia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31879415/

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 Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years Health Status: unknown Age Group: 22 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
Hypertension	1 patient Disc. AE	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years Health Status: unknown Age Group: 22 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
Vomiting	1 patient Disc. AE	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years Health Status: unknown Age Group: 22 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
Drowsiness	1 patient Disc. AE	2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years Health Status: unknown Age Group: 25 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
Dry mouth	1 patient Disc. AE	2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years Health Status: unknown Age Group: 25 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
Upset stomach	1 patient Disc. AE	2900 mg single, oral Overdose Dose: 2900 mg Route: oral Route: single Dose: 2900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years Health Status: unknown Age Group: 25 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/
Hyponatremia	grade 5, 1 patient Disc. AE	6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28816830/	unknown, 37 years Health Status: unknown Age Group: 37 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/28816830/
Seizures	grade 5, 1 patient Disc. AE	6450 mg single, oral Overdose Dose: 6450 mg Route: oral Route: single Dose: 6450 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28816830/	unknown, 37 years Health Status: unknown Age Group: 37 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/28816830/
Arrhythmia	1 patient Disc. AE	2000 mg single, oral Overdose Dose: 2000 mg Route: oral Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31879415/	unknown, 55 years Health Status: unknown Age Group: 55 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/31879415/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav3.1 7 Cav3.2 12 Cav3.3 7	CYP1A1 389 CYP1A2 1197 CYP2C8 810 CYP2C19 1119	P-gp 301

Drug as perpetrator

Target	Modality	Activity
Cav3.3 7	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17610910/	yes [IC50 23 uM]
Cav3.1 7	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17610910/	yes [IC50 43 uM]
Cav3.2 12	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17610910/	yes [IC50 45 uM]
P-gp 1932	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/11452702/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/7482685/\|https://pubmed.ncbi.nlm.nih.gov/18238857/	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. Sources: https://pubmed.ncbi.nlm.nih.gov/7482685/\|https://pubmed.ncbi.nlm.nih.gov/18238857/
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/\|https://pubmed.ncbi.nlm.nih.gov/15978881/\|https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018207s032lbl.pdf	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. Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/\|https://pubmed.ncbi.nlm.nih.gov/15978881/\|https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018207s032lbl.pdf

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/15740727/\|https://pubmed.ncbi.nlm.nih.gov/15322737/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9655	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9655
ChemicalBook	CB04633655	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB04633655
ChemicalBook	CB3376874	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3376874
ChemicalBook	CB65477609	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB65477609
eMolecules	594989	https://www.emolecules.com/cgi-bin/more?vid=594989
MolPort	MolPort-001-684-664	https://www.molport.com/shop/molecule-link/MolPort-001-684-664
Selleck Chemicals	trazodone-hydrochloride-desyrel	http://www.selleckchem.com/products/trazodone-hydrochloride-desyrel.html

PubMed

Title	Date	PubMed
New colorimetric methods for the determination of trazodone HCl, famotidine, and diltiazem HCl in their pharmaceutical dosage forms.	2003-07	12750873
A fatal drug interaction between oxycodone and clonazepam.	2003-05	12762549
Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports.	2003-05	12752037
Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone.	2003-04	12723462
Unexplained transient hyperphosphatemia is more common in acute psychiatric disorders than in acute medical-surgical conditions.	2003-03-25	12686366
[Depression in epilepsy: symptom or syndrome?].	2003-03-21	12645397
Electroanalytical characteristics of piribedil and its differential pulse and square wave voltammetric determination in pharmaceuticals and human serum.	2003-03-10	12615235
Mianserin and trazodone significantly attenuate the intensity of opioid withdrawal symptoms in mice.	2003-03	12749364
A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy.	2003-03	12655908
Assessment of the contributions of CYP3A4 and CYP3A5 in the metabolism of the antipsychotic agent haloperidol to its potentially neurotoxic pyridinium metabolite and effect of antidepressants on the bioactivation pathway.	2003-03	12584149
Pharmacologic management by clinical pharmacists of behavioral and psychological symptoms of dementia in nursing home residents: results from a pilot study.	2003-02	12587811
Association of low dose trazodone treatment with aggravated angle-closure glaucoma.	2003-02	12519465
Dissociative symptoms from combined treatment with sertraline and trazodone.	2003	12724468
Treatment of sleep disturbance in alcohol recovery: a national survey of addiction medicine physicians.	2003	12703672
Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis.	2002-12	12503813
The treatment of generalised anxiety disorder. A systematic review.	2002-12	12434110
In vitro identification of metabolic pathways and cytochrome P450 enzymes involved in the metabolism of etoperidone.	2002-11	12487725
Clitoral priapism: a rare condition presenting as a cause of vulvar pain.	2002-11	12423816
Voluntary undertaking rule and duty to warn.	2002-10-01	12374074
Voltammetric analysis of trazodone HCl in pharmaceuticals and biological fluids.	2002-09-05	12191706
Sleep in posttraumatic stress disorder.	2002-09	12585568
The pharmacologic management of SSRI-induced side effects: a survey of psychiatrists.	2002-09	12585563
Erectile dysfunction: oral pharmacotherapy options.	2002-09	12358156
Alterations in 5-HT(1A) receptors and adenylyl cyclase response by trazodone in regions of rat brain.	2002-08-16	12127910
Alpha(1)-adrenoceptor antagonists. 4. Pharmacophore-based design, synthesis, and biological evaluation of new imidazo-, benzimidazo-, and indoloarylpiperazine derivatives.	2002-08-15	12166933
Effects of trazodone and imipramine on the biological rhythm: an analysis of sleep EEG and body core temperature.	2002-08	12187365
Relationship between plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine, and its clinical effect in depressed patients.	2002-08	12142643
Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol.	2002-08	12130722
Priapism associated with trazodone in an adolescent with autism.	2002-07	12108798
Masturbatory guilt leading to severe depression and erectile dysfunction.	2002-06-27	12082666
An overview of the clinical efficacy of mirtazapine.	2002-06	12404666
Pharmacological aspects of erectile dysfunction.	2002-06	12120751
[Chronobiological research on antidepressant drugs: the effect of the antidepressant drugs, trazodone and imipramine on the circadian rhythm using electroencephalography in healthy volunteers].	2002-06	12068317
[Latest therapies for treating dementia].	2002-05-15	12031225
Paroxetine associated hepatotoxicity: a report of 3 cases and a review of the literature.	2002-05	12107856
[Progress in therapy of erectile dysfunction. New orally administered drugs].	2002-05	12085538
Psychotropic drugs and the ECG: focus on the QTc interval.	2002-05	11996627
Detecting drug-drug interactions in medication profiles of psychiatric inpatients: a two-stage approach.	2002-04	12101868
Citalopram-induced priapism.	2002-04	11939691
Serotonin releasing agents. Neurochemical, therapeutic and adverse effects.	2002-04	11888573
Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents.	2002-04	11888558
A hemodialysis patient with trazodone-induced parkinsonism.	2002-02	11818711
Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone.	2002-02	11817501
Potential interactions between herbal medicines and conventional drug therapies used by older adults attending a memory clinic.	2002	12428996
No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients.	2002	12083600
Effects of psychotropic drugs on seizure threshold.	2002	11888352
Central nervous system agents in the treatment of erectile dysfunction: how do they work?	2001-12	12084236
A display of hypomania in a depressed male in response to fluvoxamine.	2001-10	12587152
Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia?	2001-10	11890487
Successful treatment with trazodone for repetitive behavior in schizophrenia.	2001	11839140

Patents

Sample Use Guides

In Vivo Use Guide

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

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:36:59 GMT 2025` Edited by `admin` on `Mon Mar 31 17:36:59 GMT 2025`
Record UNII	YBK48BXK30
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRITTICO

Preferred Name

English

TRAZODONE

Official Name

English

1,2,4-TRIAZOLO(4,3-A)PYRIDIN-3(2H)-ONE, 2-(3-(4-(3-CHLOROPHENYL)-1-PIPERAZINYL)PROPYL)-

Systematic Name

English

TRAZODONE [VANDF]

Common Name

English

2-(3-(4-(M-CHLOROPHENYL)-1-PIPERAZINYL)PROPYL)-S-TRIAZOLO(4,3-A)PYRIDIN-3(2H)-ONE

Systematic Name

English

TRAZODONE [MI]

Common Name

English

Trazodone [WHO-DD]

Common Name

English

trazodone [INN]

Common Name

English

J10.767K

Code

English

Classification Tree Code System Code

WHO-ATC

N06AX05