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Identification
NameCyproheptadine
Accession NumberDB00434  (APRD00033)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
1-methyl-4-(5-dibenzo(a,e)cycloheptatrienylidene)piperidineNot AvailableNot Available
1-Methyl-4-(5H-dibenzo(a,d)cycloheptenylidene)piperidineNot AvailableNot Available
5-(1-methylpiperidylidene-4)-5H-dibenzo(a,d)cyclophepteneNot AvailableNot Available
AxoprolNot AvailableIS
CiproheptadinaSpanishINN
CyproheptadinGermanINN
CyproheptadineFrenchINN
CyproheptadinumLatinINN
DihexazinNot AvailableIS
GlutodinaNot AvailableIS
Salts
Name/CAS Structure Properties
Cyproheptadine Hydrochloride
Thumb
  • InChI Key: ZPMVNZLARAEGHB-UHFFFAOYSA-N
  • Monoisotopic Mass: 323.144077416
  • Average Mass: 323.859
DBSALT000625
Brand names
NameCompany
ApeplusRadicura
ApitupUniversal
BioheptBiofarm
CiplactinCipla
CipractineTeriak
CiproheptadinaArena
CiprovitNot Available
CiptadineIBN
CyheptineGreater Pharma
CyllerminCCPC
PeriactinMerck
PeriactineTeofarma
PeriatinApex
ReactinOrion
Brand mixtures
Brand NameIngredients
DynamogenCyproheptadine and Arginine
Categories
CAS number129-03-3
WeightAverage: 287.3981
Monoisotopic: 287.167399677
Chemical FormulaC21H21N
InChI KeyJJCFRYNCJDLXIK-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
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=CC=CC=C2C=CC2=CC=CC=C12
Mass Specshow(10 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassDibenzocycloheptenes
SubclassNot Available
Direct parentDibenzocycloheptenes
Alternative parentsBenzene and Substituted Derivatives; Piperidines; Tertiary Amines; Polyamines
Substituentspiperidine; benzene; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene connected by a cycloheptene ring.
Pharmacology
IndicationFor 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.
PharmacodynamicsCyproheptadine 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 actionCyproheptadine 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.
AbsorptionWell absorbed after oral administration.
Volume of distributionNot Available
Protein binding96 to 99%
Metabolism

Hepatic (cytochrome P-450 system) and some renal.

Route of eliminationAfter 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 lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.986
Caco-2 permeable + 0.8038
P-glycoprotein substrate Substrate 0.8598
P-glycoprotein inhibitor I Inhibitor 0.8563
P-glycoprotein inhibitor II Non-inhibitor 0.5315
Renal organic cation transporter Inhibitor 0.8303
CYP450 2C9 substrate Non-substrate 0.8127
CYP450 2D6 substrate Non-substrate 0.6719
CYP450 3A4 substrate Substrate 0.6092
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9082
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.902
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5433
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9511
Biodegradation Not ready biodegradable 0.8349
Rat acute toxicity 2.9576 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5429
hERG inhibition (predictor II) Inhibitor 0.7423
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers
Dosage forms
FormRouteStrength
SyrupOral
TabletOral
Prices
Unit descriptionCostUnit
Cyproheptadine hcl powder7.34USDg
Cyproheptadine HCl 4 mg tablet0.47USDtablet
Cyproheptadine 4 mg tablet0.43USDtablet
Cyproheptadine HCl 2 mg/5ml Syrup0.16USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point112.3-113-3Engelhardt, E.L.; U S . Patent 3,014,911; December 26, 1961; assigned to Merck & Co., Inc.
water solubilitySolubleNot Available
logP4.69SANGSTER (1993)
Predicted Properties
PropertyValueSource
water solubility1.36e-02 g/lALOGPS
logP5.02ALOGPS
logP4.38ChemAxon
logS-4.3ALOGPS
pKa (strongest basic)8.05ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count0ChemAxon
polar surface area3.24ChemAxon
rotatable bond count0ChemAxon
refractivity105.17ChemAxon
polarizability34.17ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Engelhardt, E.L.; U S . Patent 3,014,911; December 26, 1961; assigned to Merck & Co., Inc.

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
ResourceLink
PubChem Compound2913
PubChem Substance46508613
ChemSpider2810
BindingDB50017721
ChEBI4046
ChEMBLCHEMBL516
Therapeutic Targets DatabaseDAP000103
PharmGKBPA164749366
IUPHAR277
Guide to Pharmacology277
Drug Product Database2245668
RxListhttp://www.rxlist.com/cgi/generic2/cyprohept.htm
Drugs.comhttp://www.drugs.com/cdi/cyproheptadine.html
WikipediaCyproheptadine
ATC CodesR06AX02
AHFS Codes
  • 04:04.92
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(74.3 KB)
Interactions
Drug Interactions
Drug
DonepezilPossible antagonism of action
FluoxetinePossible antagonism of action
GalantaminePossible antagonism of action
MetyraponeThis combination renders test invalid
RivastigminePossible antagonism of action
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyproheptadine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
TriprolidineTriprolidine and Cyproheptadine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Cyproheptadine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions
  • Avoid alcohol.
  • Take with food.

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

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 receptor 2A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

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 receptor 2C

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M3 P20309 Details

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

Enzymes

1. UDP-glucuronosyltransferase 1-3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-3 P35503 Details

References:

  1. Green MD, King CD, Mojarrabi B, Mackenzie PI, Tephly TR: Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3. Drug Metab Dispos. 1998 Jun;26(6):507-12. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 10, 2014 11:16