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Protein / target

5-hydroxytryptamine receptor 2A

Encoded byHTR2AP28223Homo sapiensSwiss-Prot
UniProt: P28223Ensembl: ENSG00000102468HGNC: HGNC:5293NCBI Gene: 3356
Clinically validated
Therapeutic maturity
59
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding

Strongest disease association

Major depressive disorder

Via encoding gene HTR2A · Genetic evidence · score 0.55

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

G protein-coupled receptor for 5-hydroxytryptamine (serotonin).

View complete UniProt function annotation

G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538, PubMed:35084960). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:28129538, PubMed:35084960). HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:28129538, PubMed:35084960). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538, PubMed:35084960). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction (By similarity)

Subcellular location

Cell membraneCell projection, dendriteCell projection, axonCytoplasmic vesicleMembrane, caveolaPresynapse
Domains and Gene Ontology detail (55)

Gene Ontology

  • Caxon
  • Ccaveola
  • Ccell body fiber
  • Ccytoplasmic vesicle
  • Cdendrite
  • Cdendritic shaft
  • CG protein-coupled serotonin receptor complex
  • Cglutamatergic synapse
  • Cneurofilament
  • Cneuronal cell body
  • Cplasma membrane
  • Cpostsynaptic membrane

471 aa · 53 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Excitatory neurotransmissionGOCell proliferation & survivalGOG protein-coupled signallingUniProt · GOMuscle contractionUniProt · GOImmune signallingGO
View supporting evidence

Excitatory neurotransmission

  • ·glutamatergic synapse
  • ·negative regulation of synaptic transmission, glutamatergic

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

G protein-coupled signalling

  • ·G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:1…
  • ·G protein-coupled serotonin receptor complex
  • ·G protein-coupled serotonin receptor activity
  • ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…

Muscle contraction

  • ·G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:1…
  • ·artery smooth muscle contraction
  • ·urinary bladder smooth muscle contraction

Immune signalling

  • ·positive regulation of cytokine production involved in immune response
  • ·positive regulation of inflammatory response
View underlying pathways (2)
Serotonin receptors
G alpha (q) signalling events

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GRM2HTR2CGNAQHTR2BSLC6A4CACNA1CGNASGNA11HTR1ACACNA1DHTR2A

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

11 medicines · 10 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Schizophrenia10 medicines
aripiprazolebrexpiprazoleClozapinehaloperidolloxapineolanzapinepaliperidonepaliperidone palmitateQuetiapine FumarateRisperidone
Psychotic Disorders9 medicines
aripiprazolebrexpiprazoleClozapinehaloperidolloxapineolanzapinepaliperidonepaliperidone palmitateRisperidone
Bipolar Disorder5 medicines
aripiprazoleloxapineolanzapineQuetiapine FumarateRisperidone
Psychomotor Agitation3 medicines
aripiprazoleloxapineolanzapine
Autistic Disorder2 medicines
aripiprazoleRisperidone
Depressive Disorder2 medicines
aripiprazolemirtazapine
Mental Disorders2 medicines
loxapineolanzapine
Tourette's Syndrome2 medicines
aripiprazolehaloperidol
Conduct Disorder1 medicine
haloperidol
Sleep Initiation and Maintenance Disorders1 medicine
mirtazapine

59 medicines meet Open Targets' target-level approved-medicine definition; the 11 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

13

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Risperidone
Narrow target profileApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Autistic Disorder, Bipolar Disorder, Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Quetiapine Fumarate
Narrow target profileApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Bipolar Disorder, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Psilocybin
Narrow target profilePhase 3Agonist

Serotonin 2a (5-HT2a) receptor agonist

Direct interaction with this protein · Only this protein recorded as a target

volinanserin
Narrow target profilePhase 3Antagonist

Serotonin 2a (5-HT2a) receptor antagonist

Direct interaction with this protein · Only this protein recorded as a target

Clozapine
Narrow target profileApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

paliperidone palmitate
Narrow target profileApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

View all 13 targeting drugs
aripiprazole
Narrow target profileApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Autistic Disorder, Bipolar Disorder, Depressive Disorder, Psychomotor Agitation

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

paliperidone
Narrow target profileApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

brexpiprazole
Narrow target profileApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

olanzapine
ApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Bipolar Disorder, Mental Disorders, Psychomotor Agitation, Psychotic Disorders

Direct interaction with this protein · 1 of 5 recorded protein targets

mirtazapine
ApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Depressive Disorder, Sleep Initiation and Maintenance Disorders

Direct interaction with this protein · 1 of 5 recorded protein targets

haloperidol
ApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Conduct Disorder, Psychotic Disorders, Schizophrenia, Tourette's Syndrome

Direct interaction with this protein · 1 of 4 recorded protein targets

loxapine
ApprovedAntagonist

Serotonin 2a (5-HT2a) receptor antagonist

Indicated for Bipolar Disorder, Mental Disorders, Psychomotor Agitation, Psychotic Disorders

Direct interaction with this protein · 1 of 5 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene HTR2A

Gene-level evidence surfaced through the gene HTR2Athat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Major depressive disorder
0.92Well supported

Clinical evidence dominant · Open Targets 0.70

Schizophrenia
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Autistic Disorder
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Psychotic disorder
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Bipolar Disorder
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

View evidence synthesis (5)
Major depressive disorderWell supported
0.92
agreement 0.82–1.00
Clinical47%Genetic35%Animal model11%Literature7%

Open Targets aggregate 0.70 · 4 independent evidence families

SchizophreniaWell supported
0.77
agreement 0.61–0.92
Clinical91%Literature9%

Open Targets aggregate 0.62 · 2 independent evidence families

Autistic DisorderWell supported
0.76
agreement 0.60–0.92
Clinical94%Literature6%

Open Targets aggregate 0.62 · 2 independent evidence families

Psychotic disorderWell supported
0.76
agreement 0.60–0.91
Clinical93%Literature7%

Open Targets aggregate 0.61 · 2 independent evidence families

Bipolar DisorderWell supported
0.76
agreement 0.60–0.91
Clinical96%Literature4%

Open Targets aggregate 0.61 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Major depressive disorder0.70
Schizophrenia0.62
Autistic Disorder0.62
Psychotic disorder0.61
Bipolar Disorder0.61
Depressive Disorder0.61
bipolar I disorder0.60
Psychotic Disorders0.60

Drug development

74 compounds recorded · 59 approved · 12 in clinical development · 3 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 13 drugs that target this protein in Forefront's canonical graph (11 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
ZIMELDINEApproval
TRIFLUOPERAZINE HYDROCHLORIDEApproval
SB-773812Phase 2
BREXPIPRAZOLEApproval
HALOPERIDOL DECANOATEApproval
TEDATIOXETINEPhase 2
PALIPERIDONEApproval
CYCLOBENZAPRINEApproval
ZIPRASIDONE MESYLATEApproval
MIRTAZAPINEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

increased pupil diameterLynch et al. (2017)platelet aggregationLynch et al. (2017)hyperreflexiaLynch et al. (2017)sexual dysfunctionsClinPGxincreased sleepLynch et al. (2017)smooth muscle contractionBowes et al. (2012)adverse drug reactionsClinPGxsweatingLynch et al. (2017)increased body temperatureLynch et al. (2017)decreased memoryLynch et al. (2017)headacheClinPGxdrug abuse/dependenceLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Risperidone vs Cariprazine in Acute Mania a Head to Head Comparison of Efficacy vs TolerabilityPHASE4

NOT_YET_RECRUITING · via Risperidone · NCT07665073

Switching Medication and Augmentation Strategies for SSRI-Resistant Adolescent Depression（SMART-I): An Open-Label, Multicenter, Randomized Controlled TrialPHASE4

NOT_YET_RECRUITING · via aripiprazole · NCT07011693

Haloperidol for Pain Control in Patients With Acute Musculoskeletal Back Pain in the Emergency DepartmentPHASE4

RECRUITING · via haloperidol · NCT06395428

A Prospective, Multicenter, Randomized Controlled Trial of Fosaprepitant Combined With Tropisetron and Multi-Day Olanzapine Versus Fosaprepitant Combined With Tropisetron and Dexamethasone for the Prevention of Delayed Nausea and Vomiting Induced by High-Dose Chemotherapy in Patients Undergoing Autologous Hematopoietic Stem Cell TransplantationPHASE3

RECRUITING · via olanzapine · NCT07413809

View all trials (26)
A Randomised, Controlled Trial to Investigate the Effect of an Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.PHASE3

RECRUITING · via Clozapine · NCT05603104

Induction Protocol for Psilocybin-Assisted Therapy in Treatment-Resistant Depression (TRD): A Pilot StudyPHASE3

ACTIVE_NOT_RECRUITING · via Psilocybin · NCT06303739

Low-Dose Psilocybin Therapy for Palliative Care Patients With Chronic Cancer Pain Requiring OpioidsPHASE2

NOT_YET_RECRUITING · via Psilocybin · NCT06827054

Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use DisorderPHASE1/PHASE2

NOT_YET_RECRUITING · via Psilocybin · NCT07499583

GI-05: The Impact of Olanzapine Among Patients Receiving Neoadjuvant Chemotherapy for Gastric CancerPHASE2

NOT_YET_RECRUITING · via olanzapine · NCT07581405

Psilocybin-Assisted Massed Cognitive Processing Therapy for Chronic Posttraumatic Stress Disorder: An Open-label TrialPHASE2

RECRUITING · via Psilocybin · NCT06386003

The Efficacy of Psilocybin Therapy for Depression in Parkinson's DiseasePHASE2

NOT_YET_RECRUITING · via Psilocybin · NCT07610369

A Double-blind, Phase II Feasibility Study to Assess the Safety and Efficacy of Psilocybin Microdosing Combined With Psychotherapy in Treatment-resistant DepressionPHASE2

RECRUITING · via Psilocybin · NCT07183748

Feasibility Phase 2 Study of Psilocybin-Assisted Therapy for Opioid-Refractory Pain in Patients With Advanced CancerPHASE2

RECRUITING · via Psilocybin · NCT06001749

Mechanisms Supporting Psilocybin-assisted Psychotherapy for Alcohol Use Disorder: A Randomized, Controlled Clinical TrialPHASE2

RECRUITING · via Psilocybin · NCT05995769

Psilocybin-Assisted vs Ketamine-Assisted Psychotherapy for Alcohol Use DisorderPHASE2

ACTIVE_NOT_RECRUITING · via Psilocybin · NCT05421065

5-HT2A Agonist Psilocybin in the Treatment of Tobacco Use DisorderPHASE2

RECRUITING · via Psilocybin · NCT05452772

Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD): a Pragmatic Clinical TrialPHASE1/PHASE2

RECRUITING · via aripiprazole · NCT05814640

Evaluating the Effect of Mirtazapine on Anxiety in Parkinson's Disease Patients; a Randomized Double-blinded Placebo-controlled Clinical TrialPHASE2

RECRUITING · via mirtazapine · NCT06530290

Shortened LSD Intervention for Major Depressive DisorderPHASE1

NOT_YET_RECRUITING · via Risperidone · NCT07503002

Group Psilocybin-Assisted Therapy for Post-Traumatic Stress DisorderPHASE1

RECRUITING · via Psilocybin · NCT07506395

Exploration of Synaptotrophic Effects of Psilocybin in Opioid Use Disorder (OUD)PHASE1

RECRUITING · via Psilocybin · NCT06160284

Activating Neuroplasticity to ENHANCE the Perception Box Expanding Effects of PsilocybinPHASE1

RECRUITING · via Psilocybin · NCT05866471

Novel Pilot Study to Treat Symptoms of IBS With Diarrhea Using Combination Therapy of a Low-FODMAP Diet and a NeuromodulatorEARLY_PHASE1

RECRUITING · via mirtazapine · NCT06684470

Study of Psilocybin Assisted Psychotherapy to Address Fear of Recurrence in Patients Diagnosed With Early-stage Breast Cancer and Ovarian Cancer in RemissionPHASE1

RECRUITING · via Psilocybin · NCT06430541

Psilocybin for Treatment-Resistant Depression in Autism: a Pilot Trial With Pre-Post Brain and Cognitive Measurement to Understand MechanismPHASE1

RECRUITING · via Psilocybin · NCT06731621

Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression: An Emotional-Processing fMRI Pilot StudyPHASE1

RECRUITING · via Psilocybin · NCT06506019

A Randomized Controlled Interventional Study on the Effects of Spirulina Supplementation on Anxiety in Children With Non-Idiopathic AutismNA

NOT_YET_RECRUITING · via Risperidone · NCT07060872

VA Aripiprazole vs. Esketamine for Treatment of Depression VAST-D IIPHASE4

WITHDRAWN · via aripiprazole · NCT05554627

Clinical Study to Assess the Treatment of Schizophrenia With Paliperidone Palmitate in Rwandan Healthcare SettingsPHASE4

COMPLETED · via Risperidone · NCT04940039

Atypical Antipsychotics Influence on the Safety of the Heart and Monitoring Indicators Model BuildingPHASE4

UNKNOWN · via Risperidone · NCT04446234

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 6 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Label change2026-08-10

    Label change: OLANZAPINE (ANDA076133)

    fda · regulatory · fda · via olanzapine

  2. Label change2026-08-10

    Label change: OLANZAPINE (ANDA076255)

    fda · regulatory · fda · via olanzapine

  3. Label change2026-07-01

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  4. Regulatory approval2026-06-04

    Approval: HALOPERIDOL (ANDA214470)

    fda · regulatory · fda · via haloperidol

  5. Product recall2026-05-27

    Recall (Class II): ARIPIPRAZOLE

    fda · safety · fda · via aripiprazole

  6. New publication2026-01-02
    Psychological Therapy Quantity and Depressive Symptom Reduction in Psychedelic-Assisted Therapy: A Systematic Review and Meta-Analysis.

    JAMA network open · 2026 · 1 citation · Europe PMC · via Psilocybin

  7. New publication2025-08-05
    A dose of therapy with psilocybin - A meta-analysis of the relationship between the amount of therapy hours and treatment outcomes in psychedelic-assisted therapy.

    General hospital psychiatry · 2025 · 1 citation · Europe PMC · via Psilocybin

  8. New publication2025-06-30
    Psychedelic-Assisted Therapies for Psychosocial Symptoms in Cancer: A Systematic Review and Meta-Analysis.

    Current oncology (Toronto, Ont.) · 2025 · 2 citations · Europe PMC · via Psilocybin

  9. New publication2025-02-06
    The Therapeutic Potential of Psychedelics in Treating Substance Use Disorders: A Review of Clinical Trials.

    Medicina (Kaunas, Lithuania) · 2025 · 8 citations · Europe PMC · via Psilocybin

  10. Safety communication2023-12-18

    Drug Safety Update: Aripiprazole (Abilify and generic brands): risk of pathological gambling

    mhra · safety · mhra · via aripiprazole

  11. Safety communication2021-12-10

    Drug Safety Update: Haloperidol (Haldol): reminder of risks when used in elderly patients for the acute treatment of delirium

    mhra · safety · mhra · via haloperidol

  12. Safety communication2017-10-26

    Drug Safety Update: Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus

    mhra · safety · mhra · via Clozapine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.