Trazodone

Summary

Trazodone (CHEMBL621) is an approved small-molecule antidepressant (ATC N06AX05) targeting HTR2A, HTR2B, and HTR2C; indicated across 12 conditions including depressive disorder and insomnia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AX05
• Targets: 3 (HTR2A, HTR2B, HTR2C)
• Indications: 12 conditions
• Clinical trials: 53
• Chemistry: 371.9 Da · C19H22ClN5O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL621
Name	Trazodone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5533
ChEBI	CHEBI:9654
ATC	N06AX05
Molecular formula	C19H22ClN5O
Molecular weight	371.9
InChIKey	PHLBKPHSAVXXEF-UHFFFAOYSA-N

SMILES: C1CN(CCN1CCCN2C(=O)N3C=CC=CC3=N2)C4=CC(=CC=C4)Cl

IUPAC name: 2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-[1,2,4]triazolo[4,3-a]pyridin-3-one

ChEBI definition: An N-arylpiperazine in which one nitrogen is substituted by a 3-chlorophenyl group, while the other is substituted by a 3-(3-oxo[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)propyl group.

Pharmacological roles (ChEBI): antidepressant, sedative, adrenergic antagonist, H1-receptor antagonist, serotonin uptake inhibitor, anxiolytic drug.

Also known as: J10.767K, Trazodona, Trazodone, Trittico, trazodone, SID11111900, SID11111901, SID90341328, TRAZODONE, SID174007449

Parent form; salt/anhydrous children: CHEMBL1200798

Patent coverage: 7,138 distinct patent families (26,657 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 26,614 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
HTR2A	5-HT2A receptor	Antagonist	7.4	0%	P28223
HTR2B	5-HT2B receptor	Antagonist	7.1	0.4%	P41595
HTR2C	5-HT2C receptor	Antagonist	6.6	0%	P28335

Broader ChEMBL bioactivity targets: 36 (assay-derived). Sample: Lysine-specific demethylase 4E, Prelamin-A/C, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, D(1A) dopamine receptor.

Bioactivity

ChEMBL activities: 61 potent at pChembl ≥ 5 of 77 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	8.25	Ki	5.6	nM	CHEMBL_ACT_7792338
P14842	7.77	IC50	17	nM	CHEMBL_ACT_789374
HTR2A	7.7	IC50	20	nM	CHEMBL_ACT_7792337
HTR2A	7.61	AC50	24.4	nM	CHEMBL_ACT_25173621
HRH1	7.38	Ki	42	nM	CHEMBL_ACT_7791442
P43140	7.33	Ki	47	nM	CHEMBL_ACT_7790540
HTR2C	7.33	Ki	47	nM	CHEMBL_ACT_7792342
P15823	7.21	Ki	61	nM	CHEMBL_ACT_7790542
HTR2B	7.17	Ki	68	nM	CHEMBL_ACT_7792340
HTR2B	7.13	Ki	74	nM	CHEMBL_ACT_25629991
HTR2B	7.11	AC50	78.3	nM	CHEMBL_ACT_25164115
HTR2C	7.04	IC50	91	nM	CHEMBL_ACT_7792341
SLC6A4	6.99	Ki	102	nM	CHEMBL_ACT_7792350
HTR2B	6.97	IC50	107	nM	CHEMBL_ACT_7792339
P15823	6.96	IC50	111	nM	CHEMBL_ACT_7790541
HTR1A	6.93	Ki	118	nM	CHEMBL_ACT_24911846
P43140	6.93	IC50	117	nM	CHEMBL_ACT_7790539
ADRA1D	6.89	Ki	130	nM	CHEMBL_ACT_7790544
ADRA2B	6.75	Ki	178	nM	CHEMBL_ACT_7790548
P19327	6.75	Ki	178	nM	CHEMBL_ACT_7792334
ADRA1A	6.74	AC50	182.6	nM	CHEMBL_ACT_25137937
SLC6A4	6.72	IC50	192	nM	CHEMBL_ACT_7792349
P19327	6.65	Ki	223.9	nM	CHEMBL_ACT_828331
HTR2A	6.61	IC50	243	nM	CHEMBL_ACT_20667743
ADRA1D	6.58	IC50	265	nM	CHEMBL_ACT_7790543
HTR2B	6.56	AC50	276.9	nM	CHEMBL_ACT_25227535
P15823	6.55	IC50	281	nM	CHEMBL_ACT_118100
ADRA2C	6.55	Ki	282	nM	CHEMBL_ACT_7790550
P15823	6.55	IC50	281	nM	CHEMBL_ACT_789375
P19327	6.51	IC50	311	nM	CHEMBL_ACT_7792333

Target pathways

Aggregated over 3 target gene(s): HTR2A, HTR2B, HTR2C.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	3	HTR2A, HTR2B, HTR2C
Signaling by GPCR	3	HTR2A, HTR2B, HTR2C
Class A/1 (Rhodopsin-like receptors)	3	HTR2A, HTR2B, HTR2C
Amine ligand-binding receptors	3	HTR2A, HTR2B, HTR2C
GPCR downstream signalling	3	HTR2A, HTR2B, HTR2C
Serotonin receptors	3	HTR2A, HTR2B, HTR2C
G alpha (q) signalling events	3	HTR2A, HTR2B, HTR2C
GPCR ligand binding	3	HTR2A, HTR2B, HTR2C

Dominant GO biological processes

GO term	Targets
intracellular calcium ion homeostasis	3
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	3
phospholipase C-activating serotonin receptor signaling pathway	3
serotonin receptor signaling pathway	3
chemical synaptic transmission	3
positive regulation of phosphatidylinositol biosynthetic process	3
release of sequestered calcium ion into cytosol	3
positive regulation of ERK1 and ERK2 cascade	3
G protein-coupled serotonin receptor signaling pathway	3
signal transduction	3
G protein-coupled receptor signaling pathway	3
positive regulation of cell population proliferation	2
response to xenobiotic stimulus	2
positive regulation of fat cell differentiation	2
obsolete cGMP-mediated signaling	2

Indications & clinical

Indications

12 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
depressive disorder	4	MONDO:0002050	MONDO:0002050
insomnia	3	MONDO:0013600	EFO:0004698
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726
sleep disorder	3	MONDO:0100081	EFO:0008568
Alzheimer disease	3	MONDO:0004975	MONDO:0004975
diabetic neuropathy	2	MONDO:0006626	EFO:1000783
alcohol abuse	2	MONDO:0002046	MONDO:0007079
obstructive sleep apnea syndrome	1	MONDO:0007147	EFO:0003918
postpartum depression	1	MONDO:0005929	EFO:0007453

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 53.

Phase distribution

Phase	Trials
PHASE4	14
Not specified	10
PHASE3	9
PHASE2	8
PHASE1	7
EARLY_PHASE1	3
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02922894	PHASE4	RECRUITING	Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury
NCT05209035	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trazodone in OSA-MCI
NCT07136415	PHASE4	RECRUITING	Comparing Digital Therapy, Trazodone, and Daridorexant for Menopause-Related Insomnia Symptoms
NCT07210606	PHASE4	NOT_YET_RECRUITING	Central Apnea in Heart Failure: Physiological Mechanisms to Inform Treatment
NCT07542756	PHASE4	NOT_YET_RECRUITING	A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia
NCT00659919	PHASE4	COMPLETED	Treatment of Neuroleptic Induced Acute Akathisia With Trazodone
NCT00791739	PHASE4	COMPLETED	Trazodone and Its Augmentation With Pregabalin in the Treatment of Fibromyalgia
NCT01662297	PHASE4	TERMINATED	Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans
NCT01764867	PHASE4	UNKNOWN	Algorithm Guided Treatment Strategies for Major Depressive Disorder
NCT02118688	PHASE4	WITHDRAWN	Efficacy and Safety of Risperidone and Trazodone Monotherapy and Combination Therapy in Critically Ill Patients With Delirium
NCT03522207	PHASE4	TERMINATED	Accuracy and Efficacy of Trazodone (Desyrel) on Sleep Quality and Pain Management of TMD Patient
NCT04162743	PHASE4	COMPLETED	The Effect of Trazodone on the Severity of Obstructive Sleep Apnea in Insomnic Stroke Patients With Depression
NCT04468776	PHASE4	COMPLETED	CBT-I or Zolpidem/Trazodone for Insomnia
NCT05085808	PHASE4	WITHDRAWN	RCT: Trazodone vs Quetiapine vs Placebo for Treating ICU Delirium (TraQ)
NCT00000179	PHASE3	COMPLETED	Agitation in Alzheimer’s Disease
NCT00253890	PHASE3	COMPLETED	Insomnia and Drug Relapse Risk
NCT00775203	PHASE3	COMPLETED	A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder.
NCT01142258	PHASE3	COMPLETED	Trazodone for Sleep Disorders in Alzheimer’s Disease
NCT01468038	PHASE3	COMPLETED	A Double-blind Placebo Controlled Trial of Sentra PM, a Medical Food
NCT01524497	PHASE2/PHASE3	COMPLETED	A Clinical Study of Trazodone Hydrochloride Prolonged-Release Tablets for Treatment of Depression
NCT02086929	PHASE3	COMPLETED	Trazodone Once a Day in Major Depression Disorder
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT03534284	PHASE3	COMPLETED	Short and Long-Term Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis
NCT03668041	PHASE3	COMPLETED	National Adaptive Trial for PTSD Related Insomnia
NCT05282550	PHASE2	RECRUITING	Targeting Cognition in Early Alzheimer’s Disease by Improving Sleep With Trazodone
NCT05293600	PHASE1/PHASE2	RECRUITING	Rescue Pharmacotherapy for OSA
NCT06983080	PHASE2	RECRUITING	Efficacy of Trazodone to Treat Insomnia in Older Adults (TRADITION Study)
NCT07210112	PHASE2	NOT_YET_RECRUITING	Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)
NCT00027053	PHASE2	COMPLETED	Trazodone for Sleep Disturbance in Early Alcohol Recovery
NCT02458469	PHASE2	COMPLETED	Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in Patients With SCI
NCT03202979	PHASE2	COMPLETED	Trazodone in Painful Diabetic Neuropathy
NCT03749642	PHASE2	COMPLETED	Trazodone/Gabapentin Fixed Dose Combination Products in Painful Diabetic Neuropathy
NCT04082806	PHASE2	COMPLETED	Memory Enhancement by Gamma-hydroxybutyrate vs. Trazodone in Major Depressive Disorder.
NCT01400165	PHASE1	UNKNOWN	Comparison of the Pharmacokinetics of Three Generic Medications and Their Respective Brand Preparations
NCT02785601	PHASE1	COMPLETED	PK Study of Diet Effect of Trazodone Hydrochloride Prolonged-Released Tablets in Healthy Chinese
NCT02785614	PHASE1	COMPLETED	PK Study of Multi-dose Trazodone Hydrochloride Prolonged-released Tablets in Healthy Chinese
NCT02945644	PHASE1	SUSPENDED	Trazodone Dose Tolerance and APAP Adherence
NCT03516630	PHASE1	COMPLETED	Effects of Three Single Oral Doses of Trazodone on the QTc Interval Duration in Healthy Volunteers
NCT05136521	PHASE1	COMPLETED	Bioavailability Study of 300 mg Trazodone Hydrochloride (New Polymer) vs. 300 mg Trazodone Hydrochloride (Contramid® Prolonged-release Tablets) Under Fasting Conditions
NCT05299398	PHASE1	WITHDRAWN	Prevention of Postpartum Depression: A Pilot Placebo-controlled Trial of Trazodone

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 4 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

562 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FIDAXOMICIN	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ALOSETRON	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMIODARONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMLODIPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AMOXAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
APOMORPHINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ASENAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ATOMOXETINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AZATADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENFLUOREX	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENPERIDOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BENZTROPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
BUSPIRONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CANNABIDIOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CINACALCET	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CISAPRIDE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CITALOPRAM	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLEMASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CLOZAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CYCLIZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DAPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DASATINIB	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DESIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DESLORATADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DICYCLOMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DIMENHYDRINATE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOMPERIDONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOTHIEPIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOXAZOSIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DOXEPIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DROPERIDOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
DULOXETINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
EBASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ECONAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ENCAINIDE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
ERGOTAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FLUOXETINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C
GUANABENZ	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C