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Identification
Name Cyproheptadine
Accession Number DB00434 (APRD00033)
Type small molecule
Groups approved
Description

A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Cypoheptadine
  • Cyproheptadiene
  • Cyproheptadine Hcl
  • Dibenzosuberonone/Cyproheptadine
  • Dronactin
  • Eiproheptadine
  • Periactin
  • Periactine
  • Periactinol
  • Peritol
Brand name mixtures Not Available
Categories
  • Serotonin Antagonists
  • Antipruritics
  • Gastrointestinal Agents
  • Anti-Allergic Agents
  • Histamine H1 Antagonists
  • Antihistamine derivatives
CAS number 129-03-3
Weight Average: 287.3981
Monoisotopic: 287.167399677
Chemical Formula C21H21N
InChI Key InChIKey=JJCFRYNCJDLXIK-UHFFFAOYSA-N
InChI
InChI=1S/C21H21N/c1-22-14-12-18(13-15-22)21-19-8-4-2-6-16(19)10-11-17-7-3-5-9-20(17)21/h2-11H,12-15H2,1H3
Plain Text
IUPAC Name
1-methyl-4-{tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-2-ylidene}piperidine
SMILES
CN1CCC(CC1)=C1C2=C(C=CC=C2)C=CC2=C1C=CC=C2
Plain Text
Mass Spec show (10 KB)
Taxonomy
Kingdom Organic
Classes
  • Dibenzocycloheptenes
Substructures
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Piperidines
  • Dibenzocycloheptenes
Pharmacology
Indication For treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis due to inhalant allergens and foods, mild uncomplicated allergic skin manifestations of urticaria and angioedema, amelioration of allergic reactions to blood or plasma, cold urticaria, dermatographism, and as therapy for anaphylactic reactions adjunctive to epinephrine.
Pharmacodynamics Cyproheptadine is a piperidine antihistamine. Unlike other antihistamines, this drug also antagonizes serotonin receptors. This action makes Cyproheptadine useful in conditions such as vascular headache and anorexia. Cyproheptadine does not prevent the release of histamine but rather competes with free histamine for binding at HA-receptor sites. Cyproheptadine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Most antihistamines possess significant anticholinergic properties, but Cyproheptadine exerts only weak anticholinergic actions. Blockade of central muscarinic receptors appears to account for Cyproheptadine's antiemetic effects, although the exact mechanism is unknown. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for Cyproheptadine's ability to stimulate appetite. Cyproheptadine also has been used to counter vascular headaches, which many believe are caused by changes in serotonin activity, however it is unclear how Cyproheptadine exerts a beneficial effect on this condition.
Mechanism of action Cyproheptadine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for Cyproheptadine's ability to stimulate appetite.
Absorption Well absorbed after oral administration.
Volume of distribution Not Available
Protein binding 96 to 99%
Metabolism

Hepatic (cytochrome P-450 system) and some renal.
Route of elimination After a single 4 mg oral dose of14C-labelled cyproheptadine HCl in normal subjects, given as tablets 2% to 20% of the radioactivity was excreted in the stools. At least 40% of the administered radioactivity was excreted in the urine.
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers
Dosage forms
Form Route Strength
Syrup Oral
Tablet Oral
Prices
Unit description Cost Unit
Cyproheptadine hcl powder 7.34 USD g
Cyproheptadine HCl 4 mg tablet 0.47 USD tablet
Cyproheptadine 4 mg tablet 0.43 USD tablet
Cyproheptadine HCl 2 mg/5ml Syrup 0.16 USD ml
Patents Not Available
Properties
State solid
Melting point 215-217 oC
Experimental Properties
Property Value Source
water solubility Soluble PhysProp
logP 4.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.36e-02 g/l ALOGPS
logP 5.02 ALOGPS
logP 4.38 ChemAxon Molconvert
logS -4.33 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 3.24 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 105.17 ChemAxon Molconvert
polarizability 34.17 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. Pubmed
External Links
Resource Link
PubChem Compound 2913 Link_out
PubChem Substance 46508613 Link_out
ChemSpider 2810 Link_out
BindingDB 50017721 Link_out
ChEBI 4046 Link_out
ChEMBL 4046 Link_out
Therapeutic Targets Database DAP000103 Link_out
PharmGKB PA449169 Link_out
Drug Product Database 2245668 Link_out
RxList http://www.rxlist.com/cgi/generic2/cyprohept.htm Link_out
Drugs.com http://www.drugs.com/cdi/cyproheptadine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Cyproheptadine Link_out
ATC Codes
  • R06AX02
AHFS Codes
  • 04:04.92
PDB Entries Not Available
FDA label Not Available
MSDS show (74.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take with food.
Targets

1. Histamine H1 receptor

Pharmacological action: yes
Actions: antagonist

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rashid M, Nakazawa M, Nagatomo T: Effects of sarpogrelate, a novel 5-HT2 antagonist, on 5-HT-induced endothelium-dependent relaxations in porcine coronary artery. Jpn J Pharmacol. 2002 Aug;89(4):405-12. Pubmed
  2. Honda M, Nishida T, Ono H: Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT receptors. Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. Pubmed
  3. Callaway CW, Rempel N, Peng RY, Geyer MA: Serotonin 5-HT1-like receptors mediate hyperactivity in rats induced by 3,4-methylenedioxymethamphetamine. Neuropsychopharmacology. 1992 Sep;7(2):113-27. Pubmed
  4. Hoenicke EM, Vanecek SA, Woods JH: The discriminative stimulus effects of clozapine in pigeons: involvement of 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors. J Pharmacol Exp Ther. 1992 Oct;263(1):276-84. Pubmed
  5. Calka O, Metin A, Dulger H, Erkoc R: Effect of cyproheptadine on serum leptin levels. Adv Ther. 2005 Sep-Oct;22(5):424-8. Pubmed

3. 5-hydroxytryptamine 2C receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Honda M, Nishida T, Ono H: Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT receptors. Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. Pubmed

4. Muscarinic acetylcholine receptor M1

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Eltze M, Lambrecht G, Mutschler E: Cyproheptadine displays high affinity for muscarinic receptors but does not discriminate between receptor subtypes. Eur J Pharmacol. 1989 Dec 7;173(2-3):219-22. Pubmed

5. Muscarinic acetylcholine receptor M2

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

Organism class: human
UniProt ID: P08172 Link_out
Gene: CHRM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Eltze M, Lambrecht G, Mutschler E: Cyproheptadine displays high affinity for muscarinic receptors but does not discriminate between receptor subtypes. Eur J Pharmacol. 1989 Dec 7;173(2-3):219-22. Pubmed

6. Muscarinic acetylcholine receptor M3

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P20309 Link_out
Gene: CHRM3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Eltze M, Lambrecht G, Mutschler E: Cyproheptadine displays high affinity for muscarinic receptors but does not discriminate between receptor subtypes. Eur J Pharmacol. 1989 Dec 7;173(2-3):219-22. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:03

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.