At a glance......
Antihistamines are drugs which treat allergic rhinitis and other allergies. Antihistamines can give relief when a person has nasal congestion, sneezing, or hives because of pollen, dust mites, or animal allergy.Typically people take antihistamines as an inexpensive, generic, over-the-counter drug with few side effects.As an alternative to taking an antihistamine, people who suffer from allergies can instead avoid the substance which irritates them.Antihistamines are usually for short-term treatment.Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection.Doctors recommend that people talk to them before any longer term use of antihistamines.
H1-antihistamines refer to compounds that inhibit the activity of the H1 receptor.Since the H1 receptor exhibits constitutive activity, H1-antihistamines can be either neutral receptor antagonists or inverse agonists. Normally, histamine binds to the H1 receptor and heightens the receptor’s activity; the receptor antagonists work by binding to the receptor and blocking the activation of the receptor by histamine; by comparison, the inverse agonists bind to the receptor and reduce its activity, an effect which is opposite to histamine’s.
The vast majority of marketed H1-antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor.Clinically, H1-antihistamines are used to treat allergic reactions and mast cell-related disorders. Sedation is a common side effect of H1-antihistamines that readily cross the blood–brain barrier; some of these drugs, such as diphenhydramine and doxylamine, are therefore used to treat insomnia. H1-antihistamines can also reduce inflammation, since the expression of NF-κB, the transcription factor the regulates inflammatory processes, is promoted by both the receptor’s constitutive activity and agonist (i.e., histamine) binding at the H1 receptor.
Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system. Some second-generation antihistamines, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines.
Examples of H1 antagonists include:
- Acrivastine (see Benadryl entry in this section)
- Benadryl is a brand name for different H1 antagonist anitihistamine preparations in different regions: acrivastine is the active component of Benadryl Allergy Relief and cetirizine of Benadryl One a Day Relief in the UK; Benadryl is diphenhydramine in the US and Canada.
- Cetirizine (Zyrtec)
- Dimenhydrinate (most commonly used as an antiemetic)
- Diphenhydramine (see Benadryl entry in this section)
- Doxylamine (most commonly used as an over-the-counter drug sedative)
- Fexofenadine (Allegra)
- Hydroxyzine (Vistaril)
- Loratadine (Claritin)
- Meclizine (most commonly used as an antiemetic)
- Mirtazapine (primarily used to treat depression, also has antiemetic and appetite-stimulating effects)
- Olopatadine (used locally)
- Orphenadrine (a close relative of diphenhydramine used mainly as a skeletal muscle relaxant and anti-Parkinsons agent)
- Quetiapine (antipsychotic; trade name Seroquel)
- Rupatadine (Alergoliber)
H1 inverse agonists
The H1 receptor inverse agonists include
- Cetirizine (does not cross the blood–brain barrier)
- Desloratadine (does not cross the blood–brain barrier)
- Pyrilamine (crosses the blood–brain barrier; produces drowsiness)
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