Cyproheptadine Cyproheptadine , sold under the brand name Periactin among others, is a first-generation antihistamine with additional anticholinergic , antiserotonergic , and local anesthetic properties. It was patented in 1959 and came into medical use in 1961.Medical uses Cyproheptadine is used to treat allergic reactions . The evidence for its use for this purpose indicates its effectiveness but second generation antihistamines such as ketotifen and loratadine have shown equal results with fewer side effects . It is also used as a preventive treatment against migraine . In a 2013 study the frequency of migraine was dramatically reduced in patients within 7 to 10 days after starting treatment. The average frequency of migraine attacks in these patients before administration was 8.7 times per month, this was decreased to 3.1 times per month at 3 months after the start of treatment. 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 drug-induced hyperhidrosis , and prevention of blister formation for some people with epidermolysis bullosa simplex . One of the effects of the drug is increased appetite and weight gain, which has led to its use for this purpose in children who are wasting as well as people with cystic fibrosis . It is also 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 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 Dizziness Disturbed coordination Confusion Restlessness Excitation Nervousness Tremor Irritability Insomnia Paresthesias Neuritis Convulsions Euphoria Hallucinations Hysteria Faintness Allergic manifestation of rash and edema Diaphoresis Urticaria Photosensitivity Acute labyrinthitis Diplopia Vertigo Tinnitus Hypotension Palpitation Extrasystoles Anaphylactic shock Hemolytic anemia Blood dyscrasias such as leukopenia , agranulocytosis and thrombocytopenia Cholestasis Hepatic side effects such as: Epigastric distress Anorexia Nausea Vomiting Diarrhea Anticholinergic side effects such as: Urinary frequency Early menses Thickening of bronchial secretions Tightness of chest and wheezing Fatigue Chills Headache Increased appetite Weight gainOverdose Gastric decontamination measures such as activated charcoal are sometimes recommended in cases of overdose. The symptoms are usually indicative of CNS depression and excess anticholinergic side effects. The LD50 in mice is 123 mg/kg and 295 mg/kg in rats.Pharmacology Pharmacodynamics Cyproheptadine is a very potent antihistamine or antagonist of the H1 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-HT2 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.Pharmacokinetics Cyproheptadine is well-absorbed following oral ingestion , with peak plasma levels occurring after 1 to 3 hours. Its terminal half-life when taken orally is approximately 8 hours.Chemistry Cyproheptadine is a tricyclic benzocycloheptene and is closely related to pizotifen and ketotifen as well as to tricyclic antidepressants .Research 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. It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect. There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by SSRI and antipsychotic medications. Cyproheptadine has been studied for the treatment of posttraumatic stress disorder .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 is a second line treatment for pituitary pars intermedia dysfunction in horses.
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