Antihistamine

An antihistamine is a drug which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the histamine receptor. Only 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.

First-generation H₁-receptor antagonists

These are the oldest antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic acetylcholine receptor-antagonists (anticholinergic) agents as well. These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor-selectivity is the basis of the poor tolerability-profile of some of these agents, especially compared with the second-generation H1-antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes.

Related Topics:
Acetylcholine receptor - Anticholinergic - Adrenergic receptor - 5-HT receptor

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The first H1-antihistamine discovered was piperoxan, by Forneau and Daniel Bovet (1933) in their efforts to develop a guinea pig animal-model for anaphylaxis. Bovet went on to win the 1957 Nobel Prize in Physiology or Medicine for his contribution. Following their discovery, the first-generation H1-antihistamines were developed in the following decades. They can be classified on the basis of chemical structure, and agents within these groups have similar properties.

Related Topics:
Piperoxan - Daniel Bovet - Guinea pig - Anaphylaxis - Nobel Prize in Physiology or Medicine

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Ethylenediamines

Ethylenediamines were the first group of clinically-effective H1-antihistamines developed.

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• mepyramine (pyrilamine)
• antazoline

Ethanolamines

Diphenhydramine was the prototypical agent in this group. Significant anticholinergic adverse effects, including sedation, are observed in this group but the incidence of gastrointestnal adverse effects is relatively low. (Nelson, 2002; Rossi, 2004)

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• diphenhydramine
• carbinoxamine
• doxylamine
• clemastine
• dimenhydrinate

Alkylamines

The isomerism is a significant factor in the activity of the agents in this group. E-triprolidine, for example, is 1000-fold more potent than Z-triprolidine. This difference relates to the positioning and fit of the molecules in the histamine H1-receptor binding site. (Nelson, 2002) Alkylamines are considered to have relatively fewer sedative and gastrointestinal adverse effects, but relatively greater incidence of paradoxical CNS stimulation. (Rossi, 2004)

Related Topics:
Isomerism - CNS

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• pheniramine
• chlorphenamine (chlorpheniramine)
• dexchlorphenamine
• brompheniramine
• triprolidine

Piperazines

These compounds are structurally-related to the ethylenediamines and the ethanolamines; and produce significant anticholinergic adverse effects. Compounds from this group are often used for motion sickness, vertigo, nausea and vomiting. The second-generation H1-antihistamine cetirizine also belongs to this chemical group. (Nelson, 2002)

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• hydroxyzine
• meclizine

Tricyclics

These compounds differ from the phenothiazine antipsychotics in the ring-substitution and chain characteristics. (Nelson, 2002) They are also structurally-related to the tricyclic antidepressants, explaining the antihistaminergic adverse effects of those two drug classes and also the poor tolerability profile of tricyclic H1-antihistamines. The second-generation H1-antihistamine loratadine was derived from compounds in this group.

Related Topics:
Phenothiazine - Antipsychotic - Tricyclic antidepressant

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• promethazine
• alimemazine (trimeprazine)
• cyproheptadine
• azatadine