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AHFS/Drugs.com | Multum Consumer Information |
MedlinePlus | a600034 |
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Routes of administration | Oral |
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Pharmacokinetic data | |
Protein binding | ~96% |
Metabolism | Hepatic (CYP3A4) [1] |
Elimination half-life | 24 hours |
Excretion | Fecal |
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ECHA InfoCard | 100.065.837 |
Chemical and physical data | |
Formula | C28H31FN4O |
Molar mass | 458.581 g·mol−1 |
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Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It was withdrawn from the market globally in 1999 because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade). [2] [3]
Astemizole is a histamine H1-receptor antagonist. It has anticholinergic and antipruritic effects.
Astemizole is rapidly absorbed from the gastrointestinal tract and competitively binds to histamine H1 receptor sites in the gastrointestinal tract, uterus, blood vessels, and bronchial muscle. This suppresses the formation of edema and pruritus (caused by histamine).
Despite some earlier reports that astemizole does not cross the blood–brain barrier, several studies [4] [5] have shown high permeability and high binding to protein folds associated with Alzheimer's.
Astemizole may also act on histamine H3 receptors, thereby producing adverse effects.[ citation needed ]
Astemizole does also act as FIASMA (functional inhibitor of acid sphingomyelinase). [6]
Astemizole has been researched as a treatment for Creutzfeldt-Jakob Disease (CJD). [7]
Astemizole has an oral LD50 of approximately 2052 mg/kg (in mice).
Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells and CD34+ mast cell precursors.
Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.
H2 antagonists, sometimes referred to as H2RAs and also called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. This decreases the production of stomach acid. H2 antagonists can be used in the treatment of dyspepsia, peptic ulcers and gastroesophageal reflux disease. They have been surpassed by proton pump inhibitors (PPIs). The PPI omeprazole was found to be more effective at both healing and alleviating symptoms of ulcers and reflux oesophagitis than the H2 blockers ranitidine and cimetidine.
Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 1910, histamine has been considered a local hormone (autocoid) because it's produced without involvement of the classic endocrine glands; however, in recent years, histamine has been recognized as a central neurotransmitter. Histamine is involved in the inflammatory response and has a central role as a mediator of itching. As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues. It consists of an imidazole ring attached to an ethylamine chain; under physiological conditions, the amino group of the side-chain is protonated.
H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.
Chlorphenamine, also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis. It is taken orally. The medication takes effect within two hours and lasts for about 4–6 hours. It is a first-generation antihistamine and works by blocking the H1 receptor.
Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication. It is used in the treatment of itchiness, anxiety, insomnia, and nausea. It is used either by mouth or injection into a muscle.
The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand.
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.
Cetirizine is a second-generation antihistamine used to treat allergic rhinitis, dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty minutes and last for about a day. The degree of benefit is similar to other antihistamines such as diphenhydramine, which is a first-generation antihistamine.
Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects. Like all first-generation antihistamines, it is sedating.
Levocetirizine, sold under the brand name Xyzal, among others, is a second-generation antihistamine used for the treatment of allergic rhinitis and long-term hives of unclear cause. It is less sedating than older antihistamines. It is taken by mouth.
Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.
The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right/below) and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.
Chloropyramine is a classical first-generation antihistamine drug approved in Eastern European countries for the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions. Related indications for clinical use include angioedema, allergic reactions to insect bites, food and drug allergies, and anaphylactic shock.
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.
Antazoline is a 1st generation antihistamine with anticholinergic properties used to relieve nasal congestion and in eye drops, usually in combination with naphazoline, to relieve the symptoms of allergic conjunctivitis. To treat allergic conjunctivitis, antazoline can be combined in a solution with tetryzoline. The drug is a Histamine H1 receptor antagonist: selectively binding to but not activating the receptor, thereby blocking the actions of endogenous histamine and subsequently leading to the temporary relief of the negative symptoms brought on by histamine.
Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist, which accelerates gastric emptying throughout the whole of the gastrointestinal tract in humans, and is used for the treatment of gastritis, gastroesophageal reflux disease, functional dyspepsia and irritable bowel syndrome. It is recommended to be taken on an empty stomach (i.e. at least one hour before food or two hours after food).
Functional inhibitors of acid sphingomyelinase, or FIASMA, is a large group of pharmacological compounds inhibiting the enzyme acid sphingomyelinase. This enzyme is mainly located within the lysosome, where it cleaves sphingomyelin to ceramide and sphingosine, the latter of which is then phosphorylated to sphingosine-1-phosphate. These metabolites, and subsequent inhibition of the enzyme, influence the balance between cell death (apoptosis) and cell growth (proliferation). A lack of regulation of this sensitive equilibrium can lead to serious clinical consequences.
Anti-allergic agents are medications used to treat allergic reactions. Anti-allergic agents have existed since 3000 B.C in countries such as China and Egypt. It was not until 1933 when antihistamines, the first type of anti-allergic agents, were developed. Common allergic diseases include allergic rhinitis, allergic asthma and atopic dermatitis with varying symptoms, including runny nose, watery eyes, itchiness, coughing, and shortness of breath. More than one-third of the world's population is currently being affected by one or more allergic conditions.