A histamine antagonist is a pharmaceutical drug that inhibits the action of histamine
by either blocking its attachment to histamine receptors, or inhibiting the enzymatic activity
of histidine decarboxylase which catalyzes the transformation of histidine into histamine.
Histamine antagonists are commonly used for the relief of allergies caused by intolerance
of proteins.
Clinical effects Histamine produces increased vascular permeability,
causing fluid to escape from capillaries into tissues, which leads to the classic symptoms
of an allergic reaction — a runny nose and watery eyes.
Histamine also promotes angiogenesis.
Antihistamines suppress the histamine-induced wheal response and flare response by blocking
the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular
cells, endothelium, and mast cells.
They exert a competitive antagonism to histamines.
Itching and sneezing are suppressed by antihistamine blocking of H1-receptors on nasal sensory
nerves.
Antihistamines have also been used with great success in the treatment of Brown Recluse
spider bites as well as other arthropod bites that cause necrosis.
Clinical: H1- and H2-receptor antagonists H1-receptor antagonists
In common use, the term antihistamine refers only to compounds that inhibit action at the
H1 receptor.
Rather than "true" antagonists, H1-antihistamines are actually inverse agonists at the histamine
H1-receptor.
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.
Second-generation antihistamines cross the blood–brain barrier to a much lower degree
than the first generation antihistamines.
The main benefit is that they primarily affect peripheral histamine receptors, and therefore
are less sedating.
However, high doses can still induce the CNS drowsiness.
Examples include the following: Acrivastine
Azelastine Bilastine
Brompheniramine Buclizine
Bromodiphenhydramine Carbinoxamine
Cetirizine Chlorpromazine
Cyclizine Chlorpheniramine
Chlorodiphenhydramine Clemastine
Cyproheptadine Desloratadine
Dexbrompheniramine Dexchlorpheniramine
Dimenhydrinate Dimetindene
Diphenhydramine Doxylamine
Ebastine Embramine
Fexofenadine Hydroxyzine
Levocetirizine Loratadine
Meclozine Mirtazapine
Olopatadine Orphenadrine
Phenindamine Pheniramine
Phenyltoloxamine Promethazine
Pyrilamine Quetiapine
Rupatadine Tripelennamine
Triprolidine H2-receptor antagonists
H2 antagonists, like H1 antagonists, are also inverse agonists and not true antagonists.
They act on H2 histamine receptors found principally in the parietal cells of the gastric mucosa,
which are part of the endogenous signaling pathway for gastric acid secretion.
Normally, histamine acts on H2 to stimulate acid secretion; drugs that block H2 signaling
thus reduce the secretion of gastric acid.
H2 antagonists are among first-line therapy to treat gastrointestinal conditions including
peptic ulcers and gastroesophageal reflux disease.
Some formulations are available over the counter.
Most side effects are due to cross-reactivity with unintended receptors.
Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT
receptors at high doses.
Examples include the following: Cimetidine
Famotidine Lafutidine
Nizatidine Ranitidine
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 stimulant 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 immunomodulatory role and are being investigated as anti-inflammatory
and analgesic drugs.
H3-receptor antagonists
An H3-receptor antagonist is a classification of drugs used to block the action of histamine
at the H3 receptor.
Unlike the H1 and H2 receptors which have primarily peripheral actions, but cause sedation
if they are blocked in the brain, H3 receptors are primarily found in the brain and are inhibitory
autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine.
Histamine release in the brain triggers secondary release of excitatory neurotransmitters such
as glutamate and acetylcholine via stimulation of H1 receptors in the cerebral cortex.
Consequently unlike the H1 antagonist antihistamines which are sedating, H3 antagonists have stimulant
and nootropic effects, and are being researched as potential drugs for the treatment of neurodegenerative
conditions such as Alzheimer's disease.
Examples of selective H3 antagonists include clobenpropit, ABT-239, ciproxifan, Conessine,
and A-349,821.
Other Examples: Clobenpropit
Thioperamide H4-receptor antagonists
Examples: Thioperamide
JNJ 7777120 VUF-6002
Others Atypical antihistaminics
They inhibit the enzymatic activity of histidine decarboxylase:
tritoqualine catechin
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 include the following: Cromoglicate
Nedocromil Beta2-adrenergic agonist
References
External links Histamine antagonist at the US National Library
of Medicine Medical Subject Headings