ATC Group: R06A Antihistamines for systemic use

Acrivastine, a structural analog of triprolidine hydrochloride, exhibits H₁-antihistaminic activity in isolated tissues, animals, and humans, and has sedative effects in humans. The propionic acid derivative of acrivastine is a metabolite in several animal species (as well as in man) and also exhibits H₁-antihistaminic activity.

Alimemazine has a central sedative effect, comparable to that of chlorpromazine, but largely devoid of the latter’s antiadrenaline action. It has powerful antihistamine and anti-emetic actions. Alimemazine is used to treat neurosis, depression and anxiety of different origins. It prevents and relieves allergic conditions, which cause pruritus and urticaria by blocking histamine produced by the body during an allergic reaction. Alimemazine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding.

Antazoline is an antagonist of histamine H1 receptors. It selectively bind to but does not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

Astemizole is an antihistamine drug, used to prevent sneezing, runny nose, itching and watering of the eyes, and other allergic symptoms.

Azelastine, a phthalazinone derivative is classified as a potent long-acting anti-allergic compound with selective H₁ antagonist properties. An additional anti-inflammatory effect could be detected after topical ocular administration. Data from in vivo (pre-clinical) and in vitro studies show that azelastine inhibits the synthesis or release of the chemical mediators known to be involved in early and late stage allergic reactions e.g. leukotriene, histamine, PAF and serotonin.

Bilastine is a non-sedating, long-acting histamine antagonist with selective peripheral Η₁ receptor antagonist affinity and no affinity for muscarinic receptors.

Carbinoxamine is a histamine-H1 receptor blocking agent. It is an antihistamine with anticholinergic (drying) and sedative properties. Carbinoxamine appears to compete with histamine (type H1) for receptor sites on effector cells in the gastrointestinal tract, blood vessels and respiratory tract. Carbinoxamine is effective for the symptomatic treatment of seasonal and perennial allergic rhinitis; vasomotor rhinitis; allergic conjunctivitis due to inhalant allergens and foods; mild, uncomplicated allergic skin manifestations of urticaria and angioedema; dermatographism; as therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled.

Cetirizine, a human metabolite of hydroxyzine, is a potent and selective antagonist of peripheral H₁-receptors. In vitro receptor binding studies have shown no measurable affinity for other than Η₁-receptors.

Chlorphenamine is a potent antihistamine (H₁-antagonist). Antihistamines diminish or abolish the actions of histamine in the body by competitive reversible blockade of histamine H₁-receptor sites on tissues. Chlorphenamine also has anticholinergic activity.

Clemastine is an H₁-receptor antagonist. It inhibits selectively the histamine receptors of the H₁ type and reduces capillary permeability. It exerts a potent antihistaminic and antipruritic effect with a fast onset and long duration of action.

Cyclizine is a histamine H₁ receptor antagonist of the piperazine class which is characterised by a low incidence of drowsiness. It possesses anticholinergic and antiemetic properties. The exact mechanism by which cyclizine can prevent or suppress both nausea and vomiting from various causes is unknown.

Cyproheptadine is a first generation antihistamine which also has anticholinergic and antiserotonergic activities that is used to treat allergic conditions including seasonal rhinitis, conjunctivitis, dermatitits and urticaria.

Desloratadine is a non-sedating, long-acting histamine antagonist with selective peripheral H₁-receptor antagonist activity. After oral administration, desloratadine selectively blocks peripheral histamine Η₁-receptors because the substance is excluded from entry to the central nervous system.

Dexchlorpheniramine, the d-isomer of the racemic compound chlorpheniramine, is two times more active than chlorpheniramine. Dexchlorpheniramine does not prevent the release of histamine, but rather, competes with free histamine for binding at the H₁-receptor sites, and competitively antagonizes the effects of histamine on H₁-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Blockade of H₁-receptors also suppresses the formation of oedema, flare, and pruritus that result from histaminic activity. Since dexchlorpheniramine binds to central and peripheral H₁-receptors, sedative effects are likely to occur. Dexchlorpheniramine has high antihistaminic activity, moderate anticholinergic effects and minimal sedative effects.

Dimenhydrinate is a theoclate salt of the ethanolamine derivative diphenhydramine. It exhibits reversible competitive antagonism with histamine for the capture of H1 receptors. It has anticholinergic (antimuscarinic) properties that explain the anti-emetic action of the drug in cases of labyrinthial irritation (nausea, vertigo), and the central suppression it causes.

Dimetindene is an antihistaminic of the alkylamine group. Its action is the result of the capture of histamine Η₁ subunits. It has mild anticholinergic and sedative action.

Diphenhydramine is an ethanolamine-derivative antihistamine. It is an antihistamine with anticholinergic and marked sedative effects. It acts by inhibiting the effects on H₁-receptors. Diphenhydramine is effective in reducing sleep onset (i.e., time to fall asleep) and increasing the depth and quality of sleep.

Doxylamine, an ethanolamine, first-generation antihistamine crosses the blood-brain barrier and exerts an antiemetic action by selectively binding to H₁ receptors in the brain. Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is also a potent anticholinergic.

Ebastine has been shown to produce a rapid and long-lasting inhibition of histamine-induced effect and to have a strong affinity towards H₁-receptors.

Epinastine is a topically active, direct H₁-receptor antagonist and an inhibitor of the release of histamine from the mast cell. Epinastine is selective for the histamine H₁-receptor and has affinity for the histamine H₂receptor. Epinastine also possesses affinity for the α₁, α₂, and 5-HT₂–receptors.

Fexofenadine is a non-sedating H₁ antihistamine. Fexofenadine is a pharmacologically active metabolite of terfenadine.

Ketotifen is a histamine H₁-receptor antagonist. In vivo animal studies and in vitro studies suggest the additional activities of mast cell stabilisation and inhibition of infiltration, activation and degranulation of eosinophils.

Levocetirizine, the ® enantiomer of cetirizine, is a potent and selective antagonist of peripheral H₁-receptors. Pharmacodynamic studies in healthy volunteers demonstrate that, at half the dose, levocetirizine has comparable activity to cetirizine, both in the skin and in the nose.

Loratadine is a tricyclic antihistamine with selective, peripheral H₁-receptor activity. Loratadine has no clinically significant sedative or anticholinergic properties in the majority of the population and when used at the recommended dosage.

Meclizine is a first generation antihistamine that is used largely to treat vertigo and motion sickness.

Mepyramine is a first generation antihistamine, targeting the H1 receptor. However, it rapidly permeates the brain and so often causes drowsiness as a side effect. Mepyramine is a histamine H1 receptor inverse agonist. It binds to a G protein-coupled form of the receptor and promotes a G protein-coupled inactive state of the H1 receptor that interferes with the Gq/11-mediated signaling. Mepyramine competes with histamine for binding at H1-receptor sites on the effector cell surface, resulting in suppression of histaminic edema, flare, and pruritus. The sedative properties of mepyramine occur at the subcortical level of the CNS. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.

Mequitazine is a phenothiazine derivative with the actions and uses of antihistamines. Antihistamines diminish or abolish the main actions of histamine in the body by competitive, reversible blaockade of histamine receptor site on tissues; they do not inactivate histamine or prevent its synthesis or release. Antihistamines are used for palliative treatment of allergic reactions.

Mizolastine possesses antihistamine and antiallergic properties due to a specific and selective antagonism of peripheral histamine H₁ receptors.

Promethazine is a potent, long acting, antihistamine with additional anti-emetic central sedative and anti-cholinergic properties.

Rupatadine is a second-generation antihistamine, long-acting histamine antagonist, with selective peripheral H1-receptor antagonist activity. Some of the metabolites (desloratadine and its hydroxylated metabolites) retain an antihistaminic activity and may partially contribute to the overall efficacy of the drug.

Trimethobenzamide is used for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis. The mechanism of action of trimethobenzamide as determined in animals is obscure, but may involve the chemoreceptor trigger zone (CTZ), an area in the medulla oblongata through which emetic impulses are conveyed to the vomiting center; direct impulses to the vomiting center apparently are not similarly inhibited.