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Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.
1 Medical uses
2 Adverse effects
2.1 Overdose
3 Pharmacology
3.1 Pharmacodynamics
3.2 Pharmacokinetics
4 Chemistry
5 Research
6 Veterinary use
7 References
Medical uses
Periactin (cyproheptadine) 4 mg tablets
Cyproheptadine is used to treat allergic reactions (specifically hay fever ).
It is sometimes used, especially in its liquid formulation, as a preventive measure against migraine in children and adolescents, This use is on the label in the UK and some other countries.
It is also used off-label in the treatment of cyclical vomiting syndrome in infants; the only evidence for this use comes from retrospective studies.
Cyproheptadine is sometimes used off-label to improve akathisia in people on antipsychotic medications.
It used off-label to treat various dermatological conditions, including psychogenic itch
One of the effects of the drug is increased appetite and weight gain, which has led to its use (off-label in the USA) for this purpose in children who are wasting as well as people with cystic fibrosis.
It is sometimes used off-label 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.
Adverse effects
Adverse effects include:
Sedation and sleepiness (often transient)
Disturbed coordination
Allergic manifestation of rash and edema
Acute labyrinthitis
Diplopia (seeing double)
Hypotension (low blood pressure)
Anaphylactic shock
Hemolytic anemia
Blood dyscrasias such as leukopenia, agranulocytosis and thrombocytopenia
Hepatic (liver) side effects such as:
– Hepatitis
– Jaundice
– Hepatic failure
– Hepatic function abnormality
Epigastric distress
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
Increased appetite
Weight gain
Gastric decontamination measures such as activated charcoal are sometimes 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 LD 50 in mice is 123 mg/kg and 295 mg/kg in rats.
K i (nM)
H 1
H 2
H 3
H 4
M 1
M 2
M 3
M 4
M 5
5-HT 1A
5-HT 2A
5-HT 2B
5-HT 2C
5-HT 3
5-HT 6
5-HT 7
D 1
D 2
D 3
Values are K i (nM). The smaller the value, the more strongly the drug binds to the site.
Cyproheptadine is a very potent antihistamine or antagonist of the H 1 receptor. At higher concentrations, it also has anticholinergic, antiserotonergic, and antidopaminergic activities. Of the serotonin receptors, it is an especially potent antagonist of the 5-HT 2 receptors, and this underlies its effectiveness in the treatment of serotonin syndrome.
Cyproheptadine is known to be an antagonist or inverse agonist of all of the receptors listed in the adjacent table.
Cyproheptadine has weak antiandrogenic activity.
Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours.
Cyproheptadine is a tricyclic benzocycloheptene and is closely related to pizotifen and ketotifen as well as to tricyclic antidepressants.
Cyproheptadine was studied in one small trial as an adjunct in people with schizophrenia whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from.
There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by antipsychotics; it failed to show an effect.
Cyproheptadine has been studied for the treatment of posttraumatic stress disorder.
Veterinary use
Cyproheptadine is used in cats as an appetite stimulant
Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses.

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