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

Details

Stereochemistry ACHIRAL
Molecular Formula C19H22ClN5O
Molecular Weight 371.8645
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRAZODONE

SMILES

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

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 371.8645
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Fluoxetine-induced sexual dysfunction reversed by trazodone.
2000 Nov
Interactions between herbal medicines and prescribed drugs: a systematic review.
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
Venlafaxine- and trazodone-induced serotonin syndrome.
2001 Dec
Inhibitory presynaptic 5-hydroxytryptamine(2A) receptors regulate evoked glutamate release from rat cerebellar mossy fibers.
2001 Dec
Electroconvulsive therapy and cardiovascular complications in patients taking trazodone for insomnia.
2001 Feb
Treatment of the agitation of late-life psychosis and Alzheimer's disease.
2001 Jan
Antidepressants as analgesics: a review of randomized controlled trials.
2001 Jan
Weight outcomes among antidepressant users in nursing facilities.
2001 Jan
Fatal overdose with trazodone: case report and literature review.
2001 Jul-Aug
Possible mild serotonin syndrome related to co-prescription of tandospirone and trazodone.
2001 Mar-Apr
Effects of genetic polymorphism of CYP1A2 inducibility on the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine in depressed Japanese patients.
2001 May
Evaluation of the absorption, excretion and metabolism of [14C] etoperidone in man.
2001 Nov
The treatment of generalised anxiety disorder. A systematic review.
2002 Dec
Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone.
2002 Feb
alpha(1)-Adrenoceptor antagonists. Rational design, synthesis and biological evaluation of new trazodone-like compounds.
2002 Feb 11
Pharmacological aspects of erectile dysfunction.
2002 Jun
No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients.
2002 Summer
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
A fatal drug interaction between oxycodone and clonazepam.
2003 May
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:54:09 UTC 2021
Edited
by admin
on Sat Jun 26 05:54:09 UTC 2021
Record UNII
YBK48BXK30
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRAZODONE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
TRITTICO
Brand 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 [WHO-DD]
Common 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 [INN]
Common Name English
J10.767K
Code English
Classification Tree Code System Code
WHO-ATC N06AX05
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
WHO-VATC QN06AX05
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
LIVERTOX 991
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
NDF-RT N0000175696
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
NCI_THESAURUS C265
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
FDA ORPHAN DRUG 593917
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
Code System Code Type Description
IUPHAR
213
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
WIKIPEDIA
TRAZODONE
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
EPA CompTox
19794-93-5
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
MESH
D014196
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
DRUG CENTRAL
2717
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
DRUG BANK
DB00656
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
HSDB
7048
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
ChEMBL
CHEMBL621
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
EVMPD
SUB11224MIG
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
RXCUI
10737
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY RxNorm
CAS
19794-93-5
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
MERCK INDEX
M11010
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY Merck Index
PUBCHEM
5533
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
INN
2878
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
NCI_THESAURUS
C29510
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
FDA UNII
YBK48BXK30
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
LACTMED
Trazodone
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
ECHA (EC/EINECS)
243-317-1
Created by admin on Sat Jun 26 05:54:09 UTC 2021 , Edited by admin on Sat Jun 26 05:54:09 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE ACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC EFFECT OF FOOD
PHARMACOKINETIC
MAXIMUM TOLERATED DOSE TOXICITY
ORAL BIOAVAILABILITY PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC EXTENDED RELEASE
PHARMACOKINETIC
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
MAXIMUM TOLERATED DOSE TOXICITY
PROTEIN BINDING PHARMACOKINETIC
MAXIMUM TOLERATED DOSE TOXICITY
Route of Elimination PHARMACOKINETIC EXCRETED UNCHANGED
PHARMACOKINETIC
Route of Elimination PHARMACOKINETIC
Route of Elimination PHARMACOKINETIC