Histamine antagonist
Encyclopedia
A histamine antagonist, commonly referred to as antihistamine, is a pharmaceutical drug that inhibits action of histamine
by blocking it from attaching to histamine receptor
s.
Antihistamines suppress the histamine-induced wheal
(swelling) and vasodilation
(flare) response by blocking the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells. They effectively exert competitive antagonism of histamine for H1-receptors. Itching and sneezing are suppressed by antihistamine blockade of H1-receptors on nasal sensory nerves. Antihistamines are commonly used for relief of allergies caused by intolerances of proteins.
s at the histamine H1-receptor, rather than antagonists
per se. Clinically, H1 antagonists are used to treat allergic reactions. Sedation is a common side-effect, and some H1 antagonists, such as diphenhydramine
and doxylamine
, are also used to treat insomnia. However, second-generation antihistamines do not cross the blood-brain barrier
, and as such do not cause drowsiness.
Examples:
s and not true antagonists
. H2 histamine receptors, found principally in the parietal cell
s of the gastric
mucosa, are used to reduce the secretion of gastric acid
, treating gastrointestinal conditions including peptic ulcer
s and gastroesophageal reflux disease
.
Examples:
and nootropic
effect, and are being investigated for the treatment of conditions such as ADHD, Alzheimer's disease
, and schizophrenia
, whereas H4-antagonists appear to have an immunomodulator
y role and are being investigated as anti-inflammatory
and analgesic
drugs.
Examples:
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
by blocking it from attaching to histamine receptor
Histamine receptor
The histamine receptors are a class of G protein-coupled receptors with histamine as their endogenous ligand.There are four known histamine receptors:*H1 receptor*H2 receptor*H3 receptor*H4 receptor-Comparison:...
s.
Clinical effects
Histamines produce increased vascular permeability, causing fluid to escape from capillaries into the tissues, which leads to the classic symptoms of an allergic reaction – a runny nose and watery eyes.Antihistamines suppress the histamine-induced wheal
Wheal
Wheal may refer to:*Wheal response, a cutaneous condition left by a blow or as part of an allergic reaction*Wheal, a Cornish mine...
(swelling) and vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
(flare) response by blocking the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells. They effectively exert competitive antagonism of histamine for H1-receptors. Itching and sneezing are suppressed by antihistamine blockade of H1-receptors on nasal sensory nerves. Antihistamines are commonly used for relief of allergies caused by intolerances of proteins.
H1-receptor antagonists
In common use, the term antihistamine refers only to H1 antagonists, also known as H1 antihistamines. It has been discovered that these H1-antihistamines are actually inverse agonistInverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
s at the histamine H1-receptor, rather than antagonists
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
per se. Clinically, H1 antagonists are used to treat allergic reactions. Sedation is a common side-effect, and some H1 antagonists, such as diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
and doxylamine
Doxylamine
Doxylamine is one of the many sedating antihistamines used by itself as a short-term sedative, and in combination with other drugs as a night-time cold and allergy relief drug...
, are also used to treat insomnia. However, second-generation antihistamines do not cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
, and as such do not cause drowsiness.
Examples:
- AzelastineAzelastineAzelastine is a potent, second-generation, selective, histamine antagonist manufactured by MedaPharma. According to the Allergic Rhinitis and its Impact on Asthma treatment guidelines, intranasal anti-histamines are recommended for the first line therapy of mild intermittent, moderate/severe...
- CetirizineCetirizineCetirizine , a second-generation antihistamine, is a major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse agonist used in the treatment of allergies, hay fever, angioedema, and urticaria.-Availability:...
- CyclizineCyclizineCyclizine is an antihistamine drug used to treat nausea, vomiting and dizziness associated with motion sickness, vertigo and post-operatively following administration of general anaesthesia and opioids.-Indications:...
- Chlorpheniramine
- ClemastineClemastineClemastine, also known as meclastin, is an antihistamine and anticholinergic. Unlike loratadine or fexofenadine, clemastine is a sedating antihistamine, however it exhibits fewer other side effects than most of the widely used antihistamines. Clemastine is also classified as an antipruritic...
- DesloratadineDesloratadineDesloratadine is a drug used to treat allergies. It is marketed under several trade names such as NeoClarityn, Claramax, Clarinex, Larinex, Aerius, Dazit, Azomyr and Delot...
- DexchlorpheniramineDexchlorpheniramineDexchlorpheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria...
- DimenhydrinateDimenhydrinateDimenhydrinate is an over-the-counter drug used to prevent nausea and motion sickness...
(most commonly used as an antiemeticAntiemeticAn antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
) - DimetindeneDimetindeneDimetindene is an antihistamine/anticholinergic used orally and locally as an antipruritic....
- DiphenhydramineDiphenhydramineDiphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
(BenadrylBenadrylBenadryl is a brand name allergy medicine marketed over-the-counter by Johnson & Johnson subsidiary McNeil Consumer Healthcare. Prior to 2007, Benadryl was marketed by Pfizer Consumer Healthcare...
) - DoxylamineDoxylamineDoxylamine is one of the many sedating antihistamines used by itself as a short-term sedative, and in combination with other drugs as a night-time cold and allergy relief drug...
(most commonly used as an OTCOver-the-counter drugOver-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
sedativeSedativeA sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
) - EbastineEbastineEbastine is a non-sedating H1 antihistamine.It does not penetrate the blood-brain barrier and thus allows an effective block of the H1 receptor in peripheral tissue without a central side effect, i.e not causing sedation or drowsiness.The basic patent for ebastine in Europe is EP-B-134124...
- EmbramineEmbramineEmbramine is an antihistamine and anticholinergic....
- FexofenadineFexofenadineFexofenadine is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms...
- LevocetirizineLevocetirizineLevocetirizine is a third-generation non-sedative antihistamine, developed from the second-generation antihistamine cetirizine. Chemically, levocetirizine is the active enantiomer of cetirizine. It is the L-enantiomer of the cetirizine racemate. Levocetirizine works by blocking histamine receptors...
- LoratadineLoratadineLoratadine is a second-generation H1 histamine antagonist drug used to treat allergies. Structurally, it is closely related to tricyclic antidepressants such as imipramine, and distantly related to the atypical antipsychotic quetiapine. It is marketed by Schering-Plough under several trade names...
- MeclozineMeclozineMeclozine is an antihistamine considered to be an antiemetic. It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine . Emesafene is a combination of meclozine and pyridoxine...
(most commonly used as an antiemeticAntiemeticAn antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
) - OlopatadineOlopatadineOlopatadine hydrochloride is an antihistamine and mast cell stabilizer, sold as a prescription eye drop . It is used to treat itching associated with allergic conjunctivitis...
(used locally) - PheniraminePheniraminePheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It has relatively strong sedative effects, and may sometimes be used off-label as an over-the-counter sleeping pill in a similar manner to other sedating antihistamines...
- PromethazinePromethazinePromethazine is a first-generation antihistamine of the phenothiazine family. The drug has anti-motion sickness, antiemetic, and anticholinergic effects, as well as a strong sedative effect and in some countries is prescribed for insomnia when benzodiazepines are contraindicated...
- QuetiapineQuetiapineQuetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
(antipsychotic) - RupatadineRupatadineRupatadine is a second generation antihistamine and PAF antagonist used to treat allergies. It was discovered and developed by J. Uriach y Cia, S. A...
H2-receptor antagonists
H2 antagonists, like H1 antagonists, are also inverse agonistInverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
s and not true antagonists
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
. H2 histamine receptors, found principally in the parietal cell
Parietal cell
Parietal cells, or oxyntic cells, are the stomach epithelium cells that secrete gastric acid and intrinsic factor.Acetylcholine and gastrin . The histamine receptors act by increasing intracellular cAMP, whereas the muscarinic and gastrin receptors increase intracellular Ca2+ levels...
s of the gastric
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
mucosa, are used to reduce the secretion of gastric acid
Gastric acid
Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride...
, treating gastrointestinal conditions including peptic ulcer
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
s and gastroesophageal reflux disease
Gastroesophageal reflux disease
Gastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...
.
Examples:
- CimetidineCimetidineCimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
- FamotidineFamotidineFamotidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and it is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease . It is commonly marketed by Johnson & Johnson/Merck under the trade names Pepcidine and Pepcid and by...
- LafutidineLafutidineLafutidine is a H2 receptor antagonist....
- NizatidineNizatidineNizatidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease...
- RanitidineRanitidineRanitidine is a histamine H2-receptor antagonist that inhibits stomach acid production. It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux disease . Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions...
- RoxatidineRoxatidineRoxatidine acetate is a specific and competitive H2 receptor antagonist. The antisecretory effect of roxatidine acetate is mediated by its main metabolite, roxatidine....
Experimental: H3- and H4-receptor antagonists
These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H3-antagonists have a stimulantStimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
and nootropic
Nootropic
Nootropics , also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration...
effect, and are being investigated for the treatment of conditions such as ADHD, Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, whereas H4-antagonists appear to have an immunomodulator
Immunomodulator
An immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...
y role and are being investigated as anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
and analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
drugs.
H3-receptor antagonists
Examples:- A-349,821A-349,821A-349,821 is a potent and selective histamine H3 receptor antagonist . It has nootropic effects in animal studies, although there do not appear to be any plans for clinical development at present and it is currently only used in laboratory research....
- ABT-239ABT-239ABT-239 is an H3-receptor inverse agonist developed by Abbott. It has stimulant and nootropic effects, and has been investigated as a treatment for ADHD, Alzheimer's disease, and schizophrenia. ABT-239 is more active at the human H3 receptor than comparable agents such as thioperamide, ciproxifan,...
- CiproxifanCiproxifanCiproxifan is an extremely potent histamine H3 inverse agonist/antagonist.The histamine H3 receptor is an inhibitory autoreceptor located on histaminergic nerve terminals, and is believed to be involved in modulating the release of histamine in the brain...
- ClobenpropitClobenpropitClobenpropit is a histamine H3 receptor antagonist. It has neuroprotective effects via stimulation of GABA release in the brain....
- ThioperamideThioperamideThioperamide is a potent and selective histamine H3 antagonist that is capable of crossing the blood-brain barrier....
H4-receptor antagonists
Examples:- ThioperamideThioperamideThioperamide is a potent and selective histamine H3 antagonist that is capable of crossing the blood-brain barrier....
- JNJ 7777120JNJ 7777120JNJ-7777120 is a drug being developed by Johnson & Johnson Pharmaceutical Research & Development which acts as a potent and selective antagonist at the histamine H4 receptor. It has antiinflammatory effects, and has been demonstrated to be superior to traditional antihistamines in the treatment of...
- VUF-6002VUF-6002VUF-6002 is a drug which acts as a potent and selective antagonist at the histamine H4 receptor. It has antiinflammatory and analgesic effects in animal studies of acute inflammation....
Mast cell stabilizers
Mast cell stabilizers appear to stabilize the mast cells to prevent degranulation and mediator release. These drugs are not usually classified as histamine antagonists, but have similar indications.Examples:
- CromoglicateCromoglicateCromoglicic acid is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium...
(cromolyn) - NedocromilNedocromilNedocromil sodium is a medication used to prevent wheezing, shortness of breath, and other breathing problems caused by asthma. It is administered by an inhaler under the brand name Tilade and as an eye drop under the brand name Alocril...
- β2 adrenergic agonists