Cyproheptadine, sold under the brand name Periactin among others, is a first-generation

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

with additional

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

, antiserotonergic, and

local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...

properties. It was patented in 1959 and came into medical use in 1961.

Medical uses

Cyproheptadine is used to treat allergic reactions (specifically

hay fever Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...

). The evidence for its use for this purpose indicates its effectiveness but second generation antihistamines such as

ketotifen Ketotifen, sold under the brand name Zaditor among others, is a second-generation noncompetitive H1-antihistamine and mast cell stabilizer. It is most commonly sold as a salt with fumaric acid, ketotifen fumarate, and is available in two forms. I ...

and

loratadine Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in combination with pseudoephedrine, a decongestant, known as lora ...

have shown equal results with fewer side effects. It is also used as a preventive treatment against

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

. 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 Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and ...

in people on antipsychotic medications. It is used off-label to treat various dermatological conditions, including psychogenic itch drug-induced

hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psychologi ...

(excessive sweating), and prevention of blister formation for some people with

epidermolysis bullosa simplex Epidermolysis bullosa simplex (EBS) is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Epidermolysis bullosa s ...

. One of the effects of the drug is increased

appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to regu ...

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 Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

. It is also used off-label in the management of moderate to severe cases of

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

, a complex of symptoms associated with the use of

serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

drugs, such as

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...

s (and

monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...

), and in cases of high levels of serotonin in the blood resulting from a serotonin-producing

carcinoid A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) ...

tumor. Cyproheptadine has sedative effects and can be used to treat insomnia similarly to other centrally-acting antihistamines. The recommended dose for this use is 4 to 8 mg.

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 * Diaphoresis * Urticaria * Photosensitivity * Acute labyrinthitis * Diplopia (seeing double) * Vertigo * Tinnitus * Hypotension (low blood pressure) * Palpitation * Extrasystoles * Anaphylactic shock * Hemolytic anemia * Blood dyscrasias such as

leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...

and

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

* Cholestasis * Hepatic (liver) side effects such as: **

Hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

Jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

** Liver failure ** Hepatic function abnormality *

Epigastric In anatomy, the epigastrium (or epigastric region) is the upper central region of the abdomen. It is located between the costal margins and the subcostal plane. Pain may be referred to the epigastrium from damage to structures derived from the f ...

distress *

Anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

* Nausea * Vomiting * Diarrhea *

Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

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 "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an interv ...

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

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

of the H₁ receptor. At higher concentrations, it also has

, antiserotonergic, and

antidopaminergic A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have ...

activities. Of the

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

s, it is an especially potent antagonist of the 5-HT₂ receptors. This is thought to underlie its effectiveness in the treatment of

. 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 Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...

(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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

targets, cyproheptadine has been reported to possess weak

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...

ic activity.

Pharmacokinetics

Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours. Its

terminal half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

when taken orally is approximately 8 hours.

Chemistry

Cyproheptadine is a

tricyclic Tricyclics are chemical compounds that contain three interconnected rings of atoms. Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs. Among these are antid ...

benzocycloheptene Benzocycloheptenes are cycloheptenes with additional benzene rings attached. Most have two benzene rings, and are called dibenzocycloheptenes. Some benzocycloheptenes and substituted benzocycloheptenes have medical uses as antihistamines, antichol ...

and is closely related to

pizotifen Pizotifen ( INN) or pizotyline ( USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventive to reduce the frequency of recurrent migraine headaches. Uses The main medical use for pizotifen is ...

and

as well as to

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

Research

Cyproheptadine was studied in one small trial as an adjunct in people with

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

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 Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on ...

Veterinary use

Cyproheptadine is used in cats as an

appetite stimulant An orexigenic, or appetite stimulant, is a drug, hormone, or chemical compound, compound that increases appetite and may induce hyperphagia. This can be a medication or a naturally occurring neuropeptide hormone, such as ghrelin, orexin or neuropep ...

and as an adjunct in the treatment of

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

. Retrieved on October 26, 2008. Possible adverse effects include excitement and aggressive behavior. Retrieved on October 26, 2008. The

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of cyproheptadine in cats is 12 hours. Cyproheptadine is a second line treatment for

pituitary pars intermedia dysfunction Pituitary pars intermedia dysfunction (PPID), or equine Cushing's disease, is an endocrine disease affecting the pituitary gland of horses. It is most commonly seen in older animals, and is classically associated with the formation of a long, wavy c ...

in horses.

References

{{Authority control Antiandrogens Antihistamines Antipsychotics Appetite stimulants Dibenzocycloheptenes Dopamine antagonists Local anesthetics Muscarinic antagonists Piperidines 5-HT2 antagonists Serotonin receptor antagonists Sodium channel blockers