Paroxetine

Summary

Paroxetine (CHEMBL490) is an approved small-molecule antidepressant (ATC N06AB05) targeting P2RX4 and SLC6A4; indicated across 25 conditions including major depressive disorder and depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AB05
• Targets: 2 (P2RX4, SLC6A4)
• Indications: 25 conditions
• Clinical trials: 152
• Chemistry: 329.4 Da · C19H20FNO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL490
Name	Paroxetine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	43815
ChEBI	CHEBI:7936
ATC	N06AB05
Molecular formula	C19H20FNO3
Molecular weight	329.4
InChIKey	AHOUBRCZNHFOSL-YOEHRIQHSA-N

SMILES: C1CNC[C@H]([C@@H]1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4

IUPAC name: (3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine

ChEBI definition: A benzodioxole that consists of piperidine bearing 1,3-benzodioxol-5-yloxy)methyl and 4-fluorophenyl substituents at positions 3 and 4 respectively; the (3S,4R)-diastereomer. Highly potent and selective 5-HT uptake inhibitor that binds with high affinity to the serotonin transporter (Ki = 0.05 nM). Ki values are 1.1, 350 and 1100 nM for inhibition of [3H]-5-HT, [3H]-l-NA and [3H]-DA uptake respectively. Displays minimal affinity for α1-, α2- or β-adrenoceptors, 5-HT2A, 5-HT1A, D2 or H1 receptors at concentrations below 1000 nM, however displays weak affinity for muscarinic ACh receptors (Ki = 42 nM). Antidepressant and anxiolytic in vivo.

Pharmacological roles (ChEBI): antidepressant, anxiolytic drug, serotonin uptake inhibitor, hepatotoxic agent, P450 inhibitor.

Also known as: (-)3s,4r-paroxetine, Arketis, Arotin, Besitram, BRL 29060, BRL-29060, Casbol, Daparox, Fg-7051, Frosinor, Motivan, Parogen

Parent form; salt/anhydrous children: CHEMBL1708, CHEMBL1200609, CHEMBL1256912, CHEMBL1449490, CHEMBL1628650, CHEMBL3133300, CHEMBL6067650

Patent coverage: 12,590 distinct patent families (46,410 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 46,065 (99%) 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
P2RX4	P2X4	Antagonist	6	1.2%	Q99571
SLC6A4	SERT	Inhibition	10.1	0.7%	P31645

Broader ChEMBL bioactivity targets: 50 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, NPC intracellular cholesterol transporter 1, Ras-related protein Rab-9A, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Histamine H2 receptor, Sodium channel protein type 5 subunit alpha, Muscarinic acetylcholine receptor M5.

Bioactivity

ChEMBL activities: 118 potent at pChembl ≥ 5 of 137 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC6A4	10.4	Ki	0.04	nM	CHEMBL_ACT_1608923
SLC6A4	10.37	Ki	0.04	nM	CHEMBL_ACT_7721341
SLC6A4	10.11	Ki	0.08	nM	CHEMBL_ACT_192912
SLC6A4	10.1	Ki	0.08	nM	CHEMBL_ACT_23305411
SLC6A4	10.1	IC50	0.08	nM	CHEMBL_ACT_7721340
SLC6A4	10.05	Ki	0.09	nM	CHEMBL_ACT_1991181
SLC6A4	9.96	Ki	0.11	nM	CHEMBL_ACT_16817149
SLC6A4	9.89	Kd	0.13	nM	CHEMBL_ACT_163255
P31652	9.82	Kd	0.15	nM	CHEMBL_ACT_54524
SLC6A4	9.7	IC50	0.2	nM	CHEMBL_ACT_12723975
P31652	9.55	IC50	0.28	nM	CHEMBL_ACT_1110065
SLC6A4	9.42	Ki	0.38	nM	CHEMBL_ACT_2348898
SLC6A4	9.42	Ki	0.38	nM	CHEMBL_ACT_2571719
SLC6A4	9.38	Ki	0.42	nM	CHEMBL_ACT_2348890
SLC6A4	9.38	Ki	0.42	nM	CHEMBL_ACT_2571710
Q60857	9.36	Ki	0.44	nM	CHEMBL_ACT_195865
P31652	9.28	Ki	0.53	nM	CHEMBL_ACT_45410
P31652	9.28	Ki	0.53	nM	CHEMBL_ACT_600387
SLC6A4	9.25	IC50	0.56	nM	CHEMBL_ACT_16817101
HTR6	9.22	Ki	0.6	nM	CHEMBL_ACT_26025254
P31652	9.15	Ki	0.7	nM	CHEMBL_ACT_458601
P31652	9.14	Ki	0.73	nM	CHEMBL_ACT_163259
SLC6A4	9.1	Ki	0.8	nM	CHEMBL_ACT_27603308
P31652	8.96	Ki	1.1	nM	CHEMBL_ACT_29098209
SLC6A4	8.7	IC50	2	nM	CHEMBL_ACT_2483386
SLC6A4	8.64	AC50	2.3	nM	CHEMBL_ACT_25150920
SLC6A4	8.57	AC50	2.7	nM	CHEMBL_ACT_25150918
P31652	8.19	IC50	6.43	nM	CHEMBL_ACT_1235613
HTR6	8.15	IC50	7	nM	CHEMBL_ACT_26025306
SLC6A4	7.7	IC50	20	nM	CHEMBL_ACT_16623630

Target pathways

Aggregated over 2 target gene(s): P2RX4, SLC6A4.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter clearance	1	SLC6A4
Transmission across Chemical Synapses	1	SLC6A4
Neuronal System	1	SLC6A4
Elevation of cytosolic Ca2+ levels	1	P2RX4
Serotonin clearance from the synaptic cleft	1	SLC6A4
Platelet homeostasis	1	P2RX4
SLC-mediated transport of neurotransmitters	1	SLC6A4
Purinergic signaling in leishmaniasis infection	1	P2RX4

Dominant GO biological processes

GO term	Targets
membrane depolarization	2
tissue homeostasis	1
regulation of sodium ion transport	1
response to ischemia	1
signal transduction	1
regulation of blood pressure	1
positive regulation of calcium ion transport into cytosol	1
negative regulation of cardiac muscle hypertrophy	1
sensory perception of pain	1
calcium-mediated signaling	1
positive regulation of prostaglandin secretion	1
response to ATP	1
monoatomic ion transmembrane transport	1
response to fluid shear stress	1
purinergic nucleotide receptor signaling pathway	1

Indications & clinical

Indications

25 indications (3 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
major depressive disorder	4	MONDO:0002009	MONDO:0002009
depressive disorder	4	MONDO:0002050	MONDO:0002050
anxiety	3	MONDO:0011918	EFO:0005230
post-traumatic stress disorder	3	MONDO:0005146	EFO:0001358
panic disorder	3	MONDO:0005383	EFO:0004262
chronic hepatitis C virus infection	3	MONDO:0005354	EFO:0004220
obsessive-compulsive disorder	3	MONDO:0008114	EFO:0004242
agoraphobia	3	MONDO:0003709	EFO:1001872
social phobia	3	MONDO:0001247	EFO:1001917
dementia	3	MONDO:0001627	HP:0000726
rheumatoid arthritis	3	MONDO:0008383	EFO:0000685
neuralgia	3	MONDO:0021667	EFO:0005762
generalized anxiety disorder	3	MONDO:0001942	EFO:1001892
Parkinson disease	3	MONDO:0005180	MONDO:0005180
alcohol abuse	3	MONDO:0002046	MONDO:0007079
premature ejaculation	3	MONDO:0001780	EFO:0803321
bipolar disorder	3	MONDO:0004985	MONDO:0004985
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
myocardial infarction	2	MONDO:0005068	EFO:0000612
fibromyalgia	1	MONDO:0005546	EFO:0005687
anovulation	1	MONDO:0002775	MONDO:0002775
idiopathic pulmonary fibrosis	1	MONDO:0800504	EFO:0000768

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

Clinical trials

Total trials: 152.

Phase distribution

Phase	Trials
PHASE4	40
Not specified	35
PHASE3	30
PHASE1	24
PHASE2	19
PHASE1/PHASE2	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06799169	PHASE4	ACTIVE_NOT_RECRUITING	Management of Acute Tinnitus With Migraine Medications
NCT00018759	PHASE4	COMPLETED	Treatment Effects on Platelet Calcium in Hypertensive and Depressed Patients
NCT00025740	PHASE4	COMPLETED	Clonazepam and Paroxetine for Rapid Treatment of Post-Traumatic Stress Disorder
NCT00031317	PHASE4	COMPLETED	Evaluation of Clonazepam and Paroxetine for Panic Disorder With Depression
NCT00100464	PHASE4	COMPLETED	Serotonin and the Upper Airway in Obstructive Sleep Apnea
NCT00177567	PHASE4	COMPLETED	Treatment of Geriatric Bipolar Mood Disorders: A Pilot Study
NCT00178035	PHASE4	COMPLETED	Sleep Deprivation Plus Paroxetine for Treating Major Depression in Elderly Individuals
NCT00178048	PHASE4	COMPLETED	Paroxetine in the Treatment of Chronic Primary Insomnia
NCT00178100	PHASE4	COMPLETED	Paroxetine and Interpersonal Psychotherapy for Maintaining Health and Well-being in Elderly Individuals With Depression
NCT00225914	PHASE4	COMPLETED	Study of Paxil Use in Menopausal Women
NCT00246441	PHASE4	COMPLETED	Paroxetine for Comorbid Social Anxiety Disorder and Alcoholism
NCT00259883	PHASE4	COMPLETED	Combination Of PAXIL Tablet And Benzodiazepines
NCT00357045	PHASE4	COMPLETED	Antidepressant Prophylaxis for Interferon-Induced Depression: Efficacy of Paroxetine
NCT00429169	PHASE4	TERMINATED	Paroxetine/Bupropion in Suicide Attempters/Ideators With Major Depression
NCT00516113	PHASE4	COMPLETED	A Placebo-Controlled Study to Investigate the Onset of Action of Paroxetine in Premenstrual Dysphoria
NCT00540098	PHASE4	COMPLETED	Paroxetine vs Placebo Combined With Aerobic Exercise or Relaxation in Panic Disorder
NCT00560612	PHASE4	COMPLETED	Secondary Prevention With Paroxetine vs. Placebo in Subthreshold Posttraumatic Stress Disorder (PTSD)
NCT00594269	PHASE4	COMPLETED	Dementia Antipsychotics And Antidepressants Discontinuation Study
NCT00665678	PHASE4	TERMINATED	Neural Correlates of Early Intervention for Posttraumatic Stress Disorder (PTSD)
NCT00666757	PHASE4	COMPLETED	A Study Comparing Duloxetine to Other Antidepressants in the Treatment of Severe Depression
NCT00672776	PHASE4	COMPLETED	Effects of Paxil CR on Neural Circuits in Posttraumatic Stress Disorder (PTSD)
NCT00677352	PHASE4	COMPLETED	A Study Of Sertraline Compared With Paroxetine In The Treatment Of Panic Disorder
NCT00680602	PHASE4	COMPLETED	Group Cognitive Behavioral Therapy Versus Fluoxetine for Obsessive-Compulsive Disorder: a Practical Trial
NCT00700999	PHASE4	COMPLETED	Brain Markers of Treatment Response in Post-Traumatic Stress Disorder (PTSD)
NCT00785603	PHASE4	UNKNOWN	Paroxetines Effect on Tramadols Metabolism and Pharmakodynamics: a Dose Response Study
NCT00926835	PHASE4	TERMINATED	Effect of Antidepressants on the Treatment for Korean Major Depressive Disorder Patients
NCT01130103	PHASE4	COMPLETED	Combination Treatment for Posttraumatic Stress Disorder (PTSD) After the World Trade Center (WTC) Attack
NCT01416220	PHASE4	WITHDRAWN	Lithium Versus Paroxetine in Major Depression
NCT01681849	PHASE4	COMPLETED	Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder
NCT01764867	PHASE4	UNKNOWN	Algorithm Guided Treatment Strategies for Major Depressive Disorder
NCT02022709	PHASE4	COMPLETED	Efficacy of Exposure and Response Prevention(ERP) and SSRIs in Chinese OCD Patients
NCT02191124	PHASE4	COMPLETED	The Measurement-based Care in Patients With Depressive Disorder: A Randomized Controlled Trial
NCT02237937	PHASE4	UNKNOWN	Optimizing Antidepressant Treatment by Genotype-dependent Adjustment of Medication According to the ABCB1 Gene
NCT02273154	PHASE4	UNKNOWN	Randomized，Controlled and Open-label Study of Buspirone add-on Treatment in Patients With Major Depression Disorder
NCT02852577	PHASE4	COMPLETED	Long Term Treatment of Panic Disorder With Clonazepam or Paroxetine
NCT02932904	PHASE4	COMPLETED	Effect of Vortioxetine, Paroxetine, and Placebo on Sexual Functioning in Healthy Volunteers
NCT03149419	PHASE4	COMPLETED	Hot Flash as a Marker of Cardiovascular Risk in Recent Postmenopause: Effects of Non-hormonal Treatments
NCT03277339	PHASE4	COMPLETED	Psycho-biological Substrates of Therapeutic Benefit of Thermal Cure on Generalized Anxiety Disorders
NCT03779789	PHASE4	COMPLETED	Vortioxetine in the Elderly vs. Selective Serotonin Reuptake Inhibitors (SSRIs): a Pragmatic Assessment
NCT04404439	PHASE4	COMPLETED	Treatment of Tinnitus With Migraine Medications

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (4) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for paroxetine and CYP2D6	DPWG	CYP2D6		yes
Annotation of CPIC Guideline for paroxetine and CYP2D6	CPIC	CYP2D6	yes	yes
Annotation of CPIC Guideline for desvenlafaxine, duloxetine, fluoxetin	CPIC	HTR2A
Annotation of CPIC Guideline for citalopram, desvenlafaxine, duloxetin	CPIC	SLC6A4

PharmGKB also curates 48 clinical and 247 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.

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

Molecule	Source	Status	Shared targets
DULOXETINE	ChEMBL	Phase 4 (approved)	P2RX4, SLC6A4
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A4
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	SLC6A4
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	SLC6A4
TADALAFIL	ChEMBL + PubChem	Phase 4 (approved)	SLC6A4
TAFENOQUINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A4
UMECLIDINIUM	ChEMBL + PubChem	Phase 4 (approved)	SLC6A4
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	SLC6A4
ACRIVASTINE	ChEMBL	Phase 4 (approved)	SLC6A4
ALECTINIB	ChEMBL	Phase 4 (approved)	SLC6A4
ALLOPURINOL	ChEMBL	Phase 4 (approved)	SLC6A4
AMBENONIUM	ChEMBL	Phase 4 (approved)	SLC6A4
AMIODARONE	ChEMBL	Phase 4 (approved)	SLC6A4
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	SLC6A4
AMOXAPINE	ChEMBL	Phase 4 (approved)	SLC6A4
AMPHOTERICIN B	ChEMBL	Phase 4 (approved)	SLC6A4
APOMORPHINE	ChEMBL	Phase 4 (approved)	SLC6A4
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A4
ASENAPINE	ChEMBL	Phase 4 (approved)	SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SLC6A4
ATOMOXETINE	ChEMBL	Phase 4 (approved)	SLC6A4
ATRACURIUM	ChEMBL	Phase 4 (approved)	SLC6A4
AZATHIOPRINE	ChEMBL	Phase 4 (approved)	SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	SLC6A4
BALSALAZIDE	ChEMBL	Phase 4 (approved)	SLC6A4
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SLC6A4
BENFLUOREX	ChEMBL	Phase 4 (approved)	SLC6A4
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A4
BENZTROPINE	ChEMBL	Phase 4 (approved)	SLC6A4
BENZYDAMINE	ChEMBL	Phase 4 (approved)	SLC6A4
BEPRIDIL	ChEMBL	Phase 4 (approved)	SLC6A4
BOSUTINIB	ChEMBL	Phase 4 (approved)	SLC6A4
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A4
BROMHEXINE	ChEMBL	Phase 4 (approved)	SLC6A4
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SLC6A4
BROMPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A4
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A4
BUPROPION	ChEMBL	Phase 4 (approved)	SLC6A4
BUTENAFINE	ChEMBL	Phase 4 (approved)	SLC6A4
CABERGOLINE	ChEMBL	Phase 4 (approved)	SLC6A4
CALCIPOTRIENE	ChEMBL	Phase 4 (approved)	SLC6A4
CALCITRIOL	ChEMBL	Phase 4 (approved)	SLC6A4
CANAGLIFLOZIN	ChEMBL	Phase 4 (approved)	SLC6A4
CARBINOXAMINE	ChEMBL	Phase 4 (approved)	SLC6A4
CARIPRAZINE	ChEMBL	Phase 4 (approved)	SLC6A4
CARVEDILOL	ChEMBL	Phase 4 (approved)	SLC6A4
CEFONICID	ChEMBL	Phase 4 (approved)	SLC6A4
CELECOXIB	ChEMBL	Phase 4 (approved)	SLC6A4
CETIRIZINE	ChEMBL	Phase 4 (approved)	SLC6A4
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	SLC6A4
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A4
CHLORPHENTERMINE	ChEMBL	Phase 4 (approved)	SLC6A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	SLC6A4
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	SLC6A4
CINACALCET	ChEMBL	Phase 4 (approved)	SLC6A4
CINNARIZINE	ChEMBL	Phase 4 (approved)	SLC6A4
CISAPRIDE	ChEMBL	Phase 4 (approved)	SLC6A4
CITALOPRAM	ChEMBL	Phase 4 (approved)	SLC6A4
CLEMASTINE	ChEMBL	Phase 4 (approved)	SLC6A4