Cyproheptadine

Cyproheptadine

Systematic (IUPAC) name
4-(5H-dibenzo [a,d]cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride
Clinical data
Trade names	Periactin
AHFS/Drugs.com	monograph
MedlinePlus	a682541
Licence data	US Daily Med:link
Pregnancy category	AU: A US: B (No risk in non-human studies)
Legal status	AU: S3 (Pharmacist only) CA: OTC UK: OTC
Routes of administration	Oral
Pharmacokinetic data
Protein binding	96 to 99%
Metabolism	Hepatic
Biological half-life	8.6 hours
Excretion	Faecal (2-20%; 34% of this as unchanged drug) and renal (40%; none as unchanged drug)
Identifiers
CAS Number	129-03-3 Y Template:CAS (hydrochloride)
ATC code	R06AX02 (WHO)
PubChem	CID: 2913
IUPHAR/BPS	277
DrugBank	DB00434 Y
ChemSpider	2810 Y
UNII	2YHB6175DO Y
KEGG	D07765 Y
ChEBI	CHEBI:4046 Y
ChEMBL	CHEMBL516 Y
Chemical data
Formula	C21H21N
Molecular mass	287.398 g/mol
SMILES c43\C(=C1/CCN(C)CC1)c2ccccc2\C=C/c3cccc4
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 Y Key:JJCFRYNCJDLXIK-UHFFFAOYSA-N Y
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Cyproheptadine /ˌsaɪproʊˈhɛptədiːn/, sold under the brand name Periactin or Peritol, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.

Medical uses

Periactin (cyproheptadine) 4 mg tablets

• Cyproheptadine is used to treat allergic reactions (specifically hay fever). It is also used to treat vasomotor mucosal edema, including vasomotor rhinitis and edema of the throat.
• It has shown effectiveness in the treatment of nightmares, including those related to post-traumatic stress disorder.
• It has been used in the management of moderate to severe cases of serotonin syndrome, a complex of symptoms associated with the use of serotonergic drugs, such as selective serotonin reuptake inhibitors and monoamine oxidase inhibitors), and in cases of high levels of serotonin in the blood resulting from a serotonin-producing carcinoid tumor.
• It can also be used as a preventive measure against migraine in children and adolescents. In Australia this is the only indication for which cyproheptadine is subsidised by the PBS.
• It can relieve SSRI-induced sexual dysfunction and drug-induced hyperhidrosis (excessive sweating).
• It is also used in the treatment of cyclical vomiting syndrome
• Use of the drug can stimulate the appetite and may lead to weight gain, which is helpful for underweight people.
• According to a small study, cyproheptadine hydrochloride has been found to improve sleep, calmness, and mood and energy levels, and to improve both negative and (sometimes even) positive psychotic symptoms in a subgroup of chronic schizophrenics who did not respond (either completely or sufficiently) to other therapies.
• Cyproheptadine may improve akathisia in patients on antipsychotic medications.
• In clinical trials in which cyproheptadine was used as an adjunct to antipsychotic treatment for patients with schizophrenia, an improvement in negative symptoms was seen.

Adverse effects

Adverse effects include

• Sedation and sleepiness (often transient)
• Dizziness
• Disturbed coordination
• Confusion
• Restlessness
• Excitation
• Nervousness
• Tremor
• Irritability
• Insomnia
• Paresthesias
• Neuritis
• Convulsions
• Euphoria
• Hallucinations
• Hysteria
• Faintness
• Allergic manifestation of rash and edema
• Diphoresis
• Urticaria
• Photosensitivity
• Acute labyrinthitis
• Diplopia (seeing double)
• Vertigo
• Tinnitus
• Hypotension (low blood pressure)
• Palpitation
• Extrasystoles
• Anaphylactic shock
• Hemolytic anemia
• Blood dyscrasias such as leukopenia, agranulocytosis and thrombocytopenia
• Cholestasis
• Hepatic (liver) side effects such as:

- Hepatitis

- Jaundice

- Hepatic failure

- Hepatic function abnormality

• Epigastric distress
• Anorexia
• Nausea
• Vomiting
• Diarrhea
• Anticholinergic side effects such as:

- Blurred vision

- Constipation

- Xerostomia (dry mouth)

- Tachycardia (high heart rate)

- Urinary retention

- Difficulty passing urine

- Nasal congestion

- Nasal or throat dryness

• Urinary frequency
• Early menses
• Thickening of bronchial secretions
• Tightness of chest and wheezing
• Fatigue
• Chills
• Headache
• Increased appetite
• Weight gain

Research has shown a suppression of growth hormone with doses of 8–12 mg per day taken for 5 days.

Overdose

Supportive measures such as gastric lavage or induced emesis are usually recommended in cases of overdose. The symptoms are usually indicative of CNS depression (or conversely CNS stimulation in some) and excess anticholinergic side effects. The LD₅₀ in mice is 123 mg/kg and 295 mg/kg in rats.

Pharmacology

Cyproheptadine is known to be an antagonist (or inverse agonist depending on the site in question) of the receptors listed in the table below.

Receptor/Transporter Protein	Binding affinity (Ki[nM]) towards cloned human receptors unless otherwise specified
SERT	4100 (RC)
NET	290 (RC)
5-HT1A	59
5-HT2A	1.67
5-HT2B	1.54
5-HT2C	2.23
5-HT3	228 (MN)
5-HT6	142
5-HT7	123.01
M1	12
M2	7
M3	12
M4	8
M5	11.8
D1	117
D2	112
D3	8
H1	0.06
H3	>10000
H4	201.5

Acronyms used:
RC - Cloned rat receptor.
MN - Mouse NG108-15 receptor.

Pharmacokinetics

Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1–3 hours. Its half-life when taken orally is approximately 8 hours.

Veterinary use

Cyproheptadine is used in cats as an appetite stimulant and as an adjunct in the treatment of asthma. Possible adverse effects include excitement and aggressive behavior. The elimination half-life of cyproheptadine in cats is 12 hours.

Cyproheptadine has been used successfully in treatment of pituitary pars intermedia dysfunction in horses.

See also

• Benzocycloheptenes
• Pizotifen

• Toll-like receptor 4 investigating probable antagonistic (antiinflammatory) property of several TCA based molecules

• Pimethixene