An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during 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.
In common use, the term "antihistamine" refers only to H1 antagonists, also known as H1-receptor antagonists and H1-antihistamines. It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se.
Histamine, acting on H1-receptors, produces pruritus, vasodilatation, hypotension, flushing, headache, tachycardia, bronchoconstriction, increase in vascular permeability, potentiation of pain, and more.
While H1-antihistamines help against these effects, they work only if taken before contact with the allergen. In severe allergies, such as anaphylaxis or angioedema, these effects may be so severe as to be life-threatening. Additional administration of epinephrine, often in the form of an autoinjector (Epi-pen), is required by people with such hypersensitivities.
The authors of the American College of Chest Physicians Updates on Cough Guidelines (2006) recommend that, for cough associated with the common cold, first-generation antihistamine-decongestants are more effective than newer, non-sedating antihistamines. First-generation antihistamines include diphenhydramine (Benadryl); carbinoxamine (Clistin); clemastine (Tavist); chlorpheniramine (Chlor-Trimeton) and brompheniramine (Dimetane). However, it is important to note that a 1955 study of "antihistaminic drugs for colds," carried out by the U.S. Army Medical Corps, reported that "there was no significant difference in the proportion of cures reported by patients receiving oral antihistaminic drugs and those receiving oral placebos. Furthermore, essentially the same proportion of patients reported no benefit from either type of treatment.
The most common adverse effect is sedation; this "side-effect" is utilized in many OTC sleeping-aid preparations. Other common adverse effects in first-generation H1-antihistamines include dizziness, tinnitus, blurred vision, euphoria, uncoordination, anxiety, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough. Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination, and psychosis.
The newer second-generation H1-antihistamines are far more selective for peripheral histamine H1-receptors and have a far improved tolerability profile compared to the first-generation agents. The most common adverse effects noted for second-generation agents include drowsiness, fatigue, headache, nausea and dry mouth.
|Ethylenediamines||Ethylenediamines were the first group of clinically-effective H1-antihistamines developed.|
|Ethanolamines||Diphenhydramine was the prototypical agent in this group. Significant anticholinergic adverse effects, as well as sedation, are observed in this group but the incidence of gastrointestinal adverse effects is relatively low.|
|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. Alkylamines are considered to have relatively fewer sedative and gastrointestinal adverse effects, but relatively greater incidence of paradoxical CNS stimulation.|
|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.|
|Tricyclics and Tetracyclics||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 (and tetracyclics), explaining the H1-antihistaminergic adverse effects of those three 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.|
X = N, R1 = R2 = small alkyl groups
X = C
X = CO
Third-generation H1-antihistamines are the active enantiomer (levocetirizine) or metabolite (desloratadine & fexofenadine) derivatives of second-generation drugs intended to have increased efficacy with fewer adverse drug reactions. Indeed, fexofenadine is associated with a decreased risk of cardiac arrhythmia compared to terfenadine. However, there is little evidence for any advantage of levocetirizine or desloratadine, compared to cetirizine or loratadine, respectively.
Somaxon Present Pharmacological Data on Doxepin at the 21st European College of Neuropsychopharmacology Congress.
Sep 17, 2008; Somaxon Pharmaceuticals, Inc. (Nasdaq: SOMX), a specialty pharmaceutical company focused on the in-licensing and development of...