U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H22ClN5O.ClH
Molecular Weight 408.3254
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRAZODONE HYDROCHLORIDE

SMILES

c1ccn2c(c1)nn(CCCN3CCN(CC3)c4cccc(c4)Cl)c2=O.Cl

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

HIDE SMILES / InChI

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
17.0 nM [IC50]
223.87 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

3.78000015E11
Primary
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

3.78000015E11
Primary
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

3.78000015E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.88 μg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
13.3 μg × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
7.8 h
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

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
unknown, oral
TRAZODONE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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)
Hypertension (1 patient)
Vomiting (1 patient)
Sources:
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)
Upset stomach (1 patient)
Drowsiness (1 patient)
Sources:
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)
Hyponatremia (grade 5, 1 patient)
Sources:
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

AEs

AESignificanceDosePopulation
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

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer








Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical 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

Tox targets

PubMed

PubMed

TitleDatePubMed
Successful treatment with trazodone for repetitive behavior in schizophrenia.
2001
Interactions between herbal medicines and prescribed drugs: a systematic review.
2001
Central nervous system agents in the treatment of erectile dysfunction: how do they work?
2001 Dec
Hepatotoxicity after short-term trazodone therapy.
2001 Dec
Evaluation of the absorption, excretion and metabolism of [14C] etoperidone in man.
2001 Nov
Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia?
2001 Oct
Potential interactions between herbal medicines and conventional drug therapies used by older adults attending a memory clinic.
2002
Effects of psychotropic drugs on seizure threshold.
2002
Detecting drug-drug interactions in medication profiles of psychiatric inpatients: a two-stage approach.
2002 Apr
Citalopram-induced priapism.
2002 Apr
Serotonin releasing agents. Neurochemical, therapeutic and adverse effects.
2002 Apr
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 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
Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis.
2002 Dec
A hemodialysis patient with trazodone-induced parkinsonism.
2002 Feb
Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone.
2002 Feb
Early polyneuropharmacologic intervention in brain injury agitation.
2002 Feb
alpha(1)-Adrenoceptor antagonists. Rational design, synthesis and biological evaluation of new trazodone-like compounds.
2002 Feb 11
An 8-year-old boy with autism, 1 year later.
2002 Jan 23-30
Chronic stress impairs rotarod performance in rats: implications for depressive state.
2002 Jan-Feb
Priapism associated with trazodone in an adolescent with autism.
2002 Jul
Masturbatory guilt leading to severe depression and erectile dysfunction.
2002 Jul-Sep
An overview of the clinical efficacy of mirtazapine.
2002 Jun
Pharmacological aspects of erectile dysfunction.
2002 Jun
[Chronobiological research on antidepressant drugs: the effect of the antidepressant drugs, trazodone and imipramine on the circadian rhythm using electroencephalography in healthy volunteers].
2002 Jun
Paroxetine associated hepatotoxicity: a report of 3 cases and a review of the literature.
2002 May
[Progress in therapy of erectile dysfunction. New orally administered drugs].
2002 May
Psychotropic drugs and the ECG: focus on the QTc interval.
2002 May
[Latest therapies for treating dementia].
2002 May 15
In vitro identification of metabolic pathways and cytochrome P450 enzymes involved in the metabolism of etoperidone.
2002 Nov
Clitoral priapism: a rare condition presenting as a cause of vulvar pain.
2002 Nov
Voluntary undertaking rule and duty to warn.
2002 Oct 1
The pharmacologic management of SSRI-induced side effects: a survey of psychiatrists.
2002 Sep
Erectile dysfunction: oral pharmacotherapy options.
2002 Sep
Voltammetric analysis of trazodone HCl in pharmaceuticals and biological fluids.
2002 Sep 5
No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients.
2002 Summer
Treatment of sleep disturbance in alcohol recovery: a national survey of addiction medicine physicians.
2003
Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone.
2003 Apr
Association of low dose trazodone treatment with aggravated angle-closure glaucoma.
2003 Feb
New colorimetric methods for the determination of trazodone HCl, famotidine, and diltiazem HCl in their pharmaceutical dosage forms.
2003 Jul
Mianserin and trazodone significantly attenuate the intensity of opioid withdrawal symptoms in mice.
2003 Mar
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 Mar
Unexplained transient hyperphosphatemia is more common in acute psychiatric disorders than in acute medical-surgical conditions.
2003 Mar 25
A fatal drug interaction between oxycodone and clonazepam.
2003 May
Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports.
2003 May
Dissociative symptoms from combined treatment with sertraline and trazodone.
2003 Spring
Patents

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
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.
Name Type Language
TRAZODONE HYDROCHLORIDE
HSDB   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
TRAZODONE HYDROCHLORIDE [MART.]
Common Name English
TRAZODONE HYDROCHLORIDE [USP-RS]
Common Name English
DESYREL
Brand Name English
AF-1161
Code English
TRAZODONE HYDROCHLORIDE [MI]
Common Name English
2-(3-(4-(M-CHLOROPHENYL)-1-PIPERAZINYL)PROPYL)-S-TRIAZOLO(4,3-A)PYRIDIN-3(2H)-ONE MONOHYDROCHLORIDE
Systematic Name English
1,2,4-TRIAZOLO(4,3-A)PYRIDIN-3(2H)-ONE, 2-(3-(4-(3-CHLOROPHENYL)-1-PIPERAZINYL)PROPYL)-, MONOHYDROCHLORIDE
Common Name English
TRAZODONE HYDROCHLORIDE [VANDF]
Common Name English
TRAZODONE HYDROCHLORIDE [HSDB]
Common Name English
TRAZODONE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
TRAZODONE HYDROCHLORIDE [JAN]
Common Name English
TRAZODONE HYDROCHLORIDE [USAN]
Common Name English
TRAZODONE HCL
Common Name English
TRAZODONE HYDROCHLORIDE [WHO-DD]
Common Name English
NSC-292811
Code English
TRAZODONE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C265
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
Code System Code Type Description
CAS
25332-39-2
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
NCI_THESAURUS
C47767
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
RXCUI
82112
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY RxNorm
EPA CompTox
25332-39-2
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
DRUG BANK
DBSALT000344
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
PUBCHEM
62935
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
FDA UNII
6E8ZO8LRNM
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
ChEMBL
CHEMBL621
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
USP_CATALOG
1673500
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY USP-RS
MERCK INDEX
M11010
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
246-855-5
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
EVMPD
SUB15596MIG
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY
HSDB
25332-39-2
Created by admin on Fri Jun 25 20:56:22 UTC 2021 , Edited by admin on Fri Jun 25 20:56:22 UTC 2021
PRIMARY