as: Hepatitis Jaundice Liver 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 Overdose 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 LD50 in mice is 123 mg/kg and 295 mg/kg in rats. Pharmacology Pharmacodynamics Cyproheptadine is a very potent antihistamine or inverse agonist 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. This is thought to underlie its effectiveness in the treatment of serotonin syndrome. However, it is possible that blockade of 5-HT1 receptors may also contribute to its effectiveness in serotonin syndrome. Cyproheptadine has been reported to block 85% of 5-HT2 receptors in the human brain at a dose of 4 mg three times per day (12 mg/day total) and to block 95% of 5-HT2 receptors in the human brain at a dose of 6 mg three times per day (18 mg/day total) as measured with positron emission tomography (PET). The dose of cyproheptadine recommended to ensure blockade of the 5-HT2 receptors for serotonin syndrome is 20 to 30 mg. Besides its activity at neurotransmitter targets, cyproheptadine has been reported to possess 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