Serotonin

Summary

Serotonin (CHEMBL39) is an approved small-molecule neurotransmitter targeting HTR5A, SLC36A1, and HTR6; indicated across 1 condition.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 15 (HTR5A, SLC36A1, HTR6…)
• Indications: 1 condition
• Clinical trials: 7
• Chemistry: 176.21 Da · C10H12N2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL39
Name	Serotonin
Type	Small molecule
Max phase	3
FDA approved	yes
PubChem CID	5202
ChEBI	CHEBI:28790
Molecular formula	C10H12N2O
Molecular weight	176.21
InChIKey	QZAYGJVTTNCVMB-UHFFFAOYSA-N

SMILES: C1=CC2=C(C=C1O)C(=CN2)CCN

IUPAC name: 3-(2-aminoethyl)-1H-indol-5-ol

ChEBI definition: A primary amino compound that is the 5-hydroxy derivative of tryptamine.

Pharmacological roles (ChEBI): neurotransmitter.

Other ChEBI roles (chemical / environmental): human metabolite, mouse metabolite.

Also known as: Enteramine, Serotonin, Thrombotonin, serotonin, SID11111288, SID11111289, SID26754231, SID26754232, SID26755328, SID90341122, SID26754233, SID50109811

Parent form; salt/anhydrous children: CHEMBL535832

Patent coverage: 61,147 distinct patent families (186,160 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 178,457 (96%) 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
HTR5A	5-HT5A receptor	Full agonist	6.9	0%	P47898
SLC36A1	Proton-coupled Amino acid Transporter 1	Inhibition	2.2	0.2%	Q7Z2H8
HTR6	5-HT6 receptor	Full agonist	7.5	0.2%	P50406
HTR7	5-HT7 receptor	Full agonist	9.6	0.8%	P34969
HTR1A	5-HT1A receptor	Full agonist	9.7	0%	P08908
DRD1	D1 receptor	Partial agonist	5	0%	P21728
DRD5	D5 receptor	Full agonist	5.5	0%	P21918
HTR1B	5-HT1B receptor	Full agonist	8.4	0.2%	P28222
	5-HT3AB	Agonist	6
	5-HT3A	Agonist	6.4
HTR1D	5-HT1D receptor	Full agonist	9	0%	P28221
HTR1E	5-ht1e receptor	Full agonist	8.2	0%	P28566
HTR1F	5-HT1F receptor	Full agonist	8	0.1%	P30939
HTR2A	5-HT2A receptor	Full agonist	8.4	0%	P28223
HTR2B	5-HT2B receptor	Full agonist	8.4	0.4%	P41595
HTR2C	5-HT2C receptor	Full agonist	8.6	0%	P28335
HTR4	5-HT4 receptor	Full agonist	7	0%	Q13639

Broader ChEMBL bioactivity targets: 55 (assay-derived). Sample: Fructose-bisphosphate aldolase, ATP-dependent DNA helicase Q1, Inositol monophosphatase 1, Solute carrier family 22 member 3, 5-hydroxytryptamine receptor 1F, 5-hydroxytryptamine receptor 2B, 5-hydroxytryptamine receptor 4, Synaptic vesicular amine transporter, 5-hydroxytryptamine receptor 1B, 5-hydroxytryptamine receptor 3A.

Bioactivity

ChEMBL activities: 493 potent at pChembl ≥ 5 of 523 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2B	10.15	EC50	0.07	nM	CHEMBL_ACT_22402810
HTR2C	10.05	EC50	0.09	nM	CHEMBL_ACT_10870161
HTR2C	10.05	EC50	0.09	nM	CHEMBL_ACT_2282309
HTR7	9.96	Ki	0.11	nM	CHEMBL_ACT_13341994
HTR2C	9.92	EC50	0.12	nM	CHEMBL_ACT_25603947
HTR2C	9.9	EC50	0.13	nM	CHEMBL_ACT_25603946
HTR7	9.89	Ki	0.13	nM	CHEMBL_ACT_6317049
HTR2C	9.87	EC50	0.13	nM	CHEMBL_ACT_22451246
HTR2C	9.85	EC50	0.14	nM	CHEMBL_ACT_22451247
HTR7	9.85	Ki	0.14	nM	CHEMBL_ACT_26333237
HTR7	9.85	Ki	0.14	nM	CHEMBL_ACT_26333274
HTR2C	9.78	EC50	0.17	nM	CHEMBL_ACT_22450682
HTR7	9.77	Ki	0.17	nM	CHEMBL_ACT_17995198
HTR2C	9.77	EC50	0.17	nM	CHEMBL_ACT_18063571
HTR2C	9.77	EC50	0.17	nM	CHEMBL_ACT_22450683
P08909	9.77	EC50	0.17	nM	CHEMBL_ACT_29182698
HTR2C	9.74	EC50	0.18	nM	CHEMBL_ACT_18063556
HTR2C	9.72	EC50	0.19	nM	CHEMBL_ACT_19077838
HTR2C	9.72	EC50	0.19	nM	CHEMBL_ACT_19077940
HTR7	9.7	Ki	0.2	nM	CHEMBL_ACT_26036308
HTR2C	9.68	EC50	0.21	nM	CHEMBL_ACT_15225452
HTR7	9.66	Ki	0.22	nM	CHEMBL_ACT_2381384
HTR2A	9.64	EC50	0.23	nM	CHEMBL_ACT_25604025
HTR7	9.6	IC50	0.25	nM	CHEMBL_ACT_16501789
HTR7	9.6	IC50	0.25	nM	CHEMBL_ACT_16838459
HTR2A	9.57	EC50	0.27	nM	CHEMBL_ACT_19077966
HTR2A	9.56	EC50	0.28	nM	CHEMBL_ACT_19077906
HTR7	9.54	IC50	0.29	nM	CHEMBL_ACT_13342066
P14842	9.52	Ki	0.3	nM	CHEMBL_ACT_696603
HTR2C	9.46	EC50	0.35	nM	CHEMBL_ACT_13335522

Target pathways

Aggregated over 15 target gene(s): HTR5A, SLC36A1, HTR6, HTR7, HTR1A, DRD1, DRD5, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	12	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
Signaling by GPCR	12	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	12	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
Amine ligand-binding receptors	12	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
Serotonin receptors	12	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
GPCR ligand binding	12	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
GPCR downstream signalling	11	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
G alpha (s) signalling events	5	DRD1, DRD5, HTR4, HTR6, HTR7
G alpha (i) signalling events	5	HTR1B, HTR1D, HTR1E, HTR1F, HTR5A
G alpha (q) signalling events	3	HTR2A, HTR2B, HTR2C
Dopamine receptors	2	DRD1, DRD5
Amino acid transport across the plasma membrane	1	SLC36A1
Transport of small molecules	1	SLC36A1
R-HSA-425393	1	SLC36A1
SLC-mediated transmembrane transport	1	SLC36A1
Proton-coupled neutral amino acid transporters	1	SLC36A1
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	14
signal transduction	14
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	13
chemical synaptic transmission	13
adenylate cyclase-activating G protein-coupled receptor signaling pathway	8
G protein-coupled serotonin receptor signaling pathway	8
adenylate cyclase-inhibiting serotonin receptor signaling pathway	7
vasoconstriction	4
serotonin receptor signaling pathway	4
regulation of behavior	4
intracellular calcium ion homeostasis	4
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	4
phospholipase C-activating serotonin receptor signaling pathway	4
adenylate cyclase-activating serotonin receptor signaling pathway	3
smooth muscle contraction	3

Indications & clinical

Indications

1 indication (0 at ChEMBL trial phase 4).

The 1 indication record carries no mapped disease name (EFO/MeSH-only); none shown.

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
Not specified	5
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01697579	PHASE2	COMPLETED	Study of the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Children (MK-0517-029)
NCT01153802	PHASE1	COMPLETED	An Open Label Positron Emission Tomography Study in Healthy Male Subjects to Investigate Brain DAT and SERT Occupancy,Pharmacokinetics and Safety of Single Oral Doses of GSK1360707, Using 11C- PE2I and 11C-DASB as PET Ligands
NCT01001559	Not specified	COMPLETED	Combination Deplin® and Antidepressant Therapy for a Major Depressive Episode (MDE)- a Retrospective Analysis
NCT02669056	Not specified	COMPLETED	Brainstem and Prematurity
NCT02682004	Not specified	COMPLETED	Serotonin, Leptin and Adiponectin Level in Patients With Postpartum Depression: Controlled Study
NCT03480945	Not specified	COMPLETED	Glycemic Control and Endothelial Function in Patients With Type 2 Diabetes
NCT03576053	Not specified	COMPLETED	A Mechanistic Evaluation of the Interactions Between Thermoceptive and Pruriceptive Sensory Processing

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.

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

Molecule	Source	Status	Shared targets
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
MEBUFOTENIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
Cyproheptadine	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
ERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1D, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
PSILOCIN	ChEMBL	Phase 2	DRD1, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7
SUMATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR7
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
LYSERGIDE	ChEMBL	Phase 2	DRD5, HTR1A, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
PENFLURIDOL	ChEMBL	Phase 2	DRD1, DRD5, HTR1A, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
RITANSERIN	ChEMBL	Phase 2	DRD1, DRD5, HTR1A, HTR1B, HTR1E, HTR2A, HTR2C, HTR5A, HTR6, HTR7
AMOXAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
DOXEPIN	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
LOXAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR1B, HTR1E, HTR2A, HTR2B, HTR5A, HTR7
QUETIAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR6, HTR7
SORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD1, HTR1B, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR6, HTR7
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
YOHIMBINE	ChEMBL + PubChem	Phase 3 (approved)	DRD1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR6
METHYLERGONOVINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR6
RIZATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C
ZIPRASIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR1E, HTR2A, HTR2B, HTR2C, HTR6, HTR7
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
CINACALCET	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7
KETOTIFEN	ChEMBL	Phase 4 (approved)	DRD1, DRD5, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7
LATREPIRDINE	ChEMBL	Phase 3	HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
NIGULDIPINE	ChEMBL	Phase 2	DRD1, DRD5, HTR1A, HTR1B, HTR2C, HTR5A, HTR6, HTR7
SPIPERONE	ChEMBL	Phase 2	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
ASENAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR1E, HTR2A, HTR2B, HTR2C, HTR6
Lasmiditan	ChEMBL + PubChem	Phase 4 (approved)	DRD5, HTR1D, HTR1E, HTR1F, HTR2B, HTR5A, HTR7
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD5, HTR1B, HTR1D, HTR2A, HTR2C, HTR7
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR6
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR4, HTR7
MAPROTILINE	ChEMBL	Phase 4 (approved)	DRD1, DRD5, HTR1A, HTR2A, HTR2B, HTR2C, HTR6
METHYSERGIDE	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR6
SALMETEROL	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR7
SERTINDOLE	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR1B, HTR2A, HTR2B, HTR2C, HTR6
SUNITINIB	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR5A, HTR6
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7
THIOTHIXENE	ChEMBL	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7
GSK163090	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR7
METERGOLINE	ChEMBL	Phase 2	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7
Pyrazinamide	PubChem	Approved	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7
CANNABIDIOL	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR1E, HTR2A, HTR2B, HTR2C
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, HTR1A, HTR2A, HTR2B, HTR2C, HTR6