Cyproheptadine

Summary

Cyproheptadine (CHEMBL516) is an approved small-molecule H1-receptor antagonist (ATC R06AX02) targeting HTR6, HTR7, and ADRA1A; indicated across 6 conditions including allergic disease and severe acute respiratory syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R06AX02
• Targets: 6 (HTR6, HTR7, ADRA1A…)
• Indications: 6 conditions
• Clinical trials: 18
• Chemistry: 287.4 Da · C21H21N

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL516
Name	Cyproheptadine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2913
ChEBI	CHEBI:4046
ATC	R06AX02
Molecular formula	C21H21N
Molecular weight	287.4
InChIKey	JJCFRYNCJDLXIK-UHFFFAOYSA-N

SMILES: CN1CCC(=C2C3=CC=CC=C3C=CC4=CC=CC=C42)CC1

IUPAC name: 1-methyl-4-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenylidene)piperidine

ChEBI definition: The product resulting from the formal oxidative coupling of position 5 of 5H-dibenzo[a,d]cycloheptene with position 4 of 1-methylpiperidine resulting in the formation of a double bond between the two fragments. It is a sedating antihistamine with antimuscarinic and calcium-channel blocking actions. It is used (particularly as the hydrochloride sesquihydrate) for the relief of allergic conditions including rhinitis, conjunctivitis due to inhalant allergens and foods, urticaria and angioedema, and in pruritic skin disorders. Unlike other antihistamines, it is also a seratonin receptor antagonist, making it useful in conditions such as vascular headache and anorexia.

Pharmacological roles (ChEBI): H1-receptor antagonist, serotonergic antagonist, antipruritic drug, anti-allergic agent, gastrointestinal drug.

Also known as: Ciproheptadina, Ciprovit, Cyproheptadine, cyproheptadine, SID11110964, SID11110965, SID11113362, SID26751603, SID90341656, SID104171133, SID50100203, SID50104260

Parent form; salt/anhydrous children: CHEMBL1716

Patent coverage: 4,838 distinct patent families (17,487 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 17,418 (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
HTR6	5-HT6 receptor	Antagonist	6.8	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	6.9	0.8%	P34969
ADRA1A	α1A-adrenoceptor	Antagonist	7.4		P35348
ADRA1B	α1B-adrenoceptor	Antagonist	7.6	0%	P35368
ADRA1D	α1D-adrenoceptor	Antagonist	6.9	0.2%	P25100
HRH1	H1 receptor	Antagonist	10.2	0%	P35367

Broader ChEMBL bioactivity targets: 59 (assay-derived). Sample: 4’-phosphopantetheinyl transferase ffp, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Muscarinic acetylcholine receptor, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, Thyrotropin receptor, Muscarinic acetylcholine receptor M5.

Bioactivity

ChEMBL activities: 96 potent at pChembl ≥ 5 of 120 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	9.56	Ki	0.28	nM	CHEMBL_ACT_7710918
HRH1	9.37	Ki	0.43	nM	CHEMBL_ACT_7708765
HTR2A	9.34	Ki	0.46	nM	CHEMBL_ACT_12081324
P31389	9.27	Ki	0.54	nM	CHEMBL_ACT_260341
HTR2A	9.01	IC50	0.97	nM	CHEMBL_ACT_7710917
P31389	9	Kd	1	nM	CHEMBL_ACT_260342
HTR2C	8.89	Ki	1.28	nM	CHEMBL_ACT_7710922
HTR2B	8.82	Ki	1.5	nM	CHEMBL_ACT_25629994
P14842	8.8	Ki	1.6	nM	CHEMBL_ACT_16653630
HTR2A	8.8	Ki	1.6	nM	CHEMBL_ACT_262763
P14842	8.8	Ki	1.6	nM	CHEMBL_ACT_706893
CHRM4	8.66	Ki	2.19	nM	CHEMBL_ACT_7710842
HTR2C	8.61	IC50	2.44	nM	CHEMBL_ACT_7710921
CHRM5	8.56	Ki	2.75	nM	CHEMBL_ACT_7710844
HTR2A	8.52	Ki	3	nM	CHEMBL_ACT_411311
P08909	8.51	IC50	3.1	nM	CHEMBL_ACT_1019957
HRH1	8.43	IC50	3.7	nM	CHEMBL_ACT_7708764
CHRM5	8.42	IC50	3.83	nM	CHEMBL_ACT_7710843
P08482	8.4	Ki	4	nM	CHEMBL_ACT_1153253
CHRM1	8.4	Ki	3.94	nM	CHEMBL_ACT_7710836
P14842	8.3	Ki	5	nM	CHEMBL_ACT_1274564
CHRM2	8.24	AC50	5.7	nM	CHEMBL_ACT_25195587
HTR2B	8.22	Ki	6.01	nM	CHEMBL_ACT_7710920
P08909	8.1	Kd	7.94	nM	CHEMBL_ACT_861768
HTR2B	8.03	IC50	9.44	nM	CHEMBL_ACT_7710919
CHRM3	8.02	Ki	9.65	nM	CHEMBL_ACT_7710840
P34968	7.96	Ki	11	nM	CHEMBL_ACT_262764
HTR2C	7.96	Ki	11	nM	CHEMBL_ACT_411312
CHRM2	7.92	Ki	12	nM	CHEMBL_ACT_7710838
DRD3	7.8	Ki	16	nM	CHEMBL_ACT_7708735

Target pathways

Aggregated over 6 target gene(s): HTR6, HTR7, ADRA1A, ADRA1B, ADRA1D, HRH1.

Top Reactome pathways

13 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	5	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
Signaling by GPCR	5	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	5	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
Amine ligand-binding receptors	5	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
GPCR downstream signalling	5	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
GPCR ligand binding	5	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
G alpha (q) signalling events	4	ADRA1A, ADRA1B, ADRA1D, HRH1
Adrenoceptors	3	ADRA1A, ADRA1B, ADRA1D
G alpha (12/13) signalling events	3	ADRA1A, ADRA1B, ADRA1D
Serotonin receptors	2	HTR6, HTR7
G alpha (s) signalling events	2	HTR6, HTR7
Histamine receptors	1	HRH1
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
signal transduction	6
G protein-coupled receptor signaling pathway	6
phospholipase C-activating G protein-coupled receptor signaling pathway	4
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	3
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	3
chemical synaptic transmission	3
positive regulation of cytosolic calcium ion concentration	3
cell-cell signaling	3
positive regulation of MAPK cascade	3
positive regulation of vasoconstriction	3
adenylate cyclase-activating adrenergic receptor signaling pathway	3
neuron-glial cell signaling	3
adrenergic receptor signaling pathway	3
adenylate cyclase-activating serotonin receptor signaling pathway	2
G protein-coupled serotonin receptor signaling pathway	2

Indications & clinical

Indications

6 indications (1 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
allergic disease	4	MONDO:0005271	MONDO:0005271
severe acute respiratory syndrome	3	MONDO:0005091	MONDO:0100096
mitral valve insufficiency	2	MONDO:1030008	HP:0001653
alcohol abuse	2	MONDO:0002046	MONDO:0007079
stroke disorder	0	MONDO:0005098	EFO:0000712

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

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
PHASE4	5
PHASE2	5
PHASE3	2
EARLY_PHASE1	2
Not specified	2
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06751290	PHASE4	ACTIVE_NOT_RECRUITING	The Use of Cyproheptadine in Pediatric Feeding Disorders
NCT01314989	PHASE4	UNKNOWN	Cyproheptadine as an Appetite Stimulant
NCT01940978	PHASE4	COMPLETED	A Study of Combination Therapy in Children With ADHD
NCT02568007	PHASE4	TERMINATED	Effects of Cyproheptadine on Growth and Behavior in Pediatric Feeding Disorders
NCT05087381	PHASE4	COMPLETED	Randomized-controlled Trial of the Effectiveness of COVID-19 Early Treatment in Community
NCT04820751	PHASE3	UNKNOWN	Cyproheptadine in Severe COVID-19 : A Unblinded Randomized Trial
NCT04979221	PHASE3	UNKNOWN	Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients With COVID-19
NCT06175273	PHASE2/PHASE3	COMPLETED	Pediatric Oncology Nutrition Intervention Trial
NCT04488081	PHASE2	ACTIVE_NOT_RECRUITING	I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients
NCT01076283	PHASE2	COMPLETED	A Study on the Biobehavioral Mechanisms of Baclofen and Alcohol Drinking
NCT01675050	PHASE2	TERMINATED	A Placebo-controlled Crossover Trial Using Cyproheptadine To Treat Children With Functional Abdominal Pain
NCT04108104	PHASE2	COMPLETED	Clinical Outcome of a Patented Pharmaceutical Composition (KT-110) to Treat Alcohol Use Disorder While Avoiding Major Side Effects
NCT04876573	PHASE2	UNKNOWN	Pilot Study for Cyproheptadine in Hospitalized Patient for COVID-19
NCT06147622	PHASE1	COMPLETED	A Study to Assess the Pharmacokinetic Profile of Prazosin and Cyproheptadine
NCT01688570	EARLY_PHASE1	COMPLETED	Mechanisms of Neuromuscular Fatigue Post Stroke
NCT03593811	EARLY_PHASE1	COMPLETED	Noninvasive Markers of Functional Nausea in Children
NCT01538693	Not specified	COMPLETED	Molecular Markers of Neuroplasticity During Exercise in People With Incomplete Spinal Cord Injury
NCT02418949	Not specified	COMPLETED	Altering Activation Patterns Post-stroke

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
CLOZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
NEFAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
OLANZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
QUETIAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
RISPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
VILAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
LATREPIRDINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
NIGULDIPINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
SPIRAMIDE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6, HTR7
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR7
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
BUSPIRONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR7
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
CISAPRIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR7
DOXEPIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
EBASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
KETOTIFEN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
MIANSERIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
PROMAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
SERTINDOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6
SILODOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR7
TEGASEROD	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
TERFENADINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR6
THIORIDAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
FANANSERIN	ChEMBL	Phase 2	ADRA1A, ADRA1B, HRH1, HTR6, HTR7
IPSAPIRONE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D, HTR6, HTR7
METERGOLINE	ChEMBL	Phase 2	ADRA1A, ADRA1D, HRH1, HTR6, HTR7
PIZOTYLINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D, HRH1, HTR7
RITANSERIN	ChEMBL	Phase 2	ADRA1A, ADRA1B, HRH1, HTR6, HTR7
SPIPERONE	ChEMBL	Phase 2	ADRA1A, ADRA1B, HRH1, HTR6, HTR7
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR7
Pyrazinamide	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, HRH1, HTR6, HTR7
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR6
BENZTROPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR6, HTR7
CINACALCET	ChEMBL	Phase 4 (approved)	ADRA1B, HRH1, HTR6, HTR7
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6
CLONIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR7
DEXMEDETOMIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR7
DIBENZEPIN	ChEMBL	Phase 4 (approved)	ADRA1A, HRH1, HTR6, HTR7
HYDROXYZINE	ChEMBL	Phase 4 (approved)	ADRA1A, HRH1, HTR6, HTR7
IMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, HRH1, HTR6, HTR7
KETANSERIN	ChEMBL	Phase 4 (approved)	ADRA1A, HRH1, HTR6, HTR7
LOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, HRH1, HTR6, HTR7
MAPROTILINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6
MEPAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HRH1, HTR6
METHYSERGIDE	ChEMBL	Phase 4 (approved)	ADRA1A, HRH1, HTR6, HTR7
MOXISYLYTE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HRH1