TRAZODONE HYDROCHLORIDE

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

Structure Search

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

HIDE SMILES / InChI

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 231 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703	Agonist 2678	17.0 nM [IC50]
Serotonin (5-HT) receptor 34 Target ID: CHEMBL2096904 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9986703	Agonist 2678
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8568799	Agonist 2678	223.87 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Major depressive disorder 173 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022411lbl.pdf	Primary	Approved 8429	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 108 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 272 Sources: https://clinicaltrials.gov/ct2/show/NCT00000179	Primary	Phase III 656	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 Co-administed with:: methyltestosterone(200 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 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 Co-administed with:: alprazolam(8 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 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 n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 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 n = 1 Health Status: unknown Age Group: 55 years Sex: F Population Size: 1 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 Co-administed with:: methyltestosterone(200 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 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 Co-administed with:: methyltestosterone(200 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 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 Co-administed with:: methyltestosterone(200 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 22 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 22 years Sex: M Population Size: 1 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 Co-administed with:: alprazolam(8 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 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 Co-administed with:: alprazolam(8 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 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 Co-administed with:: alprazolam(8 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/6838028/	unknown, 25 years n = 1 Health Status: unknown Condition: suicide attempt Age Group: 25 years Sex: F Population Size: 1 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 n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 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 n = 1 Health Status: unknown Condition: suicide attempt Age Group: 37 years Sex: F Population Size: 1 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 n = 1 Health Status: unknown Age Group: 55 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/31879415/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav3.1 7 Cav3.2 12 Cav3.3 7	CYP1A1 349 CYP1A2 1054 CYP2C8 693 CYP2C19 991	P-gp 257

Drug as perpetrator

Target	Modality	Activity
Cav3.3 7	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17610910/	yes [IC50 23 uM]
Cav3.1 7	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17610910/	yes [IC50 43 uM]
Cav3.2 12	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17610910/	yes [IC50 45 uM]
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/11452702/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9616194/	no
CYP2D6 1217	substrate 3367 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 1737	substrate 3367 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 1647	inhibitor 1626 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
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
eMolecules	594989	https://www.emolecules.com/cgi-bin/more?vid=594989

PubMed

Title	Date	PubMed
The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea.	2001	11686898
Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective.	2001	11524025
The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5-HT3 receptor antagonism.	2001 Apr	11526964
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	11352540
Misdiagnosis of myoclonus in antidepressant induced serotonin excess.	2001 Dec	11758001
Recommendations for the management of behavioral and psychological symptoms of dementia.	2001 Feb	11237317
Screening for detection of new antidepressants, neuroleptics, hypnotics, and their metabolites in urine by GC-MS developed using rat liver microsomes.	2001 Feb	11206046
Treatment of the agitation of late-life psychosis and Alzheimer's disease.	2001 Jan	11520475
Weight outcomes among antidepressant users in nursing facilities.	2001 Jan	11207842
Serotonin syndrome. A common but often unrecognized psychiatric condition.	2001 Jan	11196339
Survey on the usefulness of trazodone in patients with PTSD with insomnia or nightmares.	2001 Jul	11518472
Pharmacology of erectile function and dysfunction.	2001 May	11402577
Evaluation of the absorption, excretion and metabolism of [14C] etoperidone in man.	2001 Nov	11765144
A display of hypomania in a depressed male in response to fluvoxamine.	2001 Oct	12587152
Antidepressant drug prescribing in Italy, 2000: analysis of a general practice database.	2001 Oct	11758640
Spectrophotometric, spectrofluorimetric and LC determination of trazodone hydrochloride.	2001 Sep	11470198
Citalopram-induced priapism.	2002 Apr	11939691
Effects of trazodone and imipramine on the biological rhythm: an analysis of sleep EEG and body core temperature.	2002 Aug	12187365
Relationship between plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine, and its clinical effect in depressed patients.	2002 Aug	12142643
Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol.	2002 Aug	12130722
Alpha(1)-adrenoceptor antagonists. 4. Pharmacophore-based design, synthesis, and biological evaluation of new imidazo-, benzimidazo-, and indoloarylpiperazine derivatives.	2002 Aug 15	12166933
Alterations in 5-HT(1A) receptors and adenylyl cyclase response by trazodone in regions of rat brain.	2002 Aug 16	12127910
Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone.	2002 Feb	11817501
[Progress in therapy of erectile dysfunction. New orally administered drugs].	2002 May	12085538
[Depression in epilepsy: symptom or syndrome?].	2002 Nov-Dec	12645397
Voluntary undertaking rule and duty to warn.	2002 Oct 1	12374074
Sleep in posttraumatic stress disorder.	2002 Sep	12585568
Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone.	2003 Apr	12723462
Pharmacologic management by clinical pharmacists of behavioral and psychological symptoms of dementia in nursing home residents: results from a pilot study.	2003 Feb	12587811
Electroanalytical characteristics of piribedil and its differential pulse and square wave voltammetric determination in pharmaceuticals and human serum.	2003 Mar 10	12615235
Unexplained transient hyperphosphatemia is more common in acute psychiatric disorders than in acute medical-surgical conditions.	2003 Mar 25	12686366
Dissociative symptoms from combined treatment with sertraline and trazodone.	2003 Spring	12724468

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.

Name

Type

Language

TRAZODONE HYDROCHLORIDE

Official Name

English

Trazodone hydrochloride [WHO-DD]

Common 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

NSC-292811

Code

English

TRAZODONE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C265