Histamine is a substance released by the body's immune system from cells called mast cells. This occurs in response to injury or allergies. Histamine receptors are the proteins on cells found in the brain, blood vessels, lungs, skin and stomach that bind to histamine in order to produce an inflammatory response. The symptoms of the inflammatory response are red and watery eyes, swelling of the body, itching, rash or wheal and flare of the skin, stomach upset, congestion and runny nose, along with sneezing, coughing, and shortness of breath. Histamine blockers, or antihistamines, are medications that prevent the binding of histamine to its receptors within the body, and thereby inhibit or lessen these symptoms. Three types of histamine receptors are affected by these drugs called H1-, H2-, and H3--receptors. While H1-receptors are more widespread in the body, H2-receptors are found largely in the stomach and H3-receptors are in the brain. H1-blockers prevent or reduce severe allergic reactions, allergy-induced runny nose called allergic rhinitis, sinus congestion, and rash. H2-blockers decrease heartburn-related conditions like acid reflux called gastroesophageal reflux disease or GERD, where acid or food regurgitates back from the stomach into the throat, and peptic ulcers, which are sores in the stomach's lining resulting from excessive secretion of stomach acid. H3-blockers are still being studied in conditions involving the brain and sleep. (see references 5, 7 and 9).
First-generation Histamine H1-receptor Blockers
In order to alleviate allergy symptoms, the first-generation H1-blockers were developed, beginning with the drug diphenhydramine (Benadryl). Other medications in this class include chlorpheneramine (Chlor-trimeton) and hydroxyzine (Vistaril). H1-receptor blockers work on preventing sinus congestion, seasonal allergies, nausea, itching, and the wheal and flare reaction of the skin.In addition, intravenous or injectable diphenhydramine is often used in the hospital-setting to treat severe allergic reactions such as anaphylaxis. The side effects of these medications include drowsiness, stomach upset, increased heart rate, dry mouth, blurred vision, and confusion. Another class of drugs that block H1-receptors are the tricyclic antidepressants or TCAs, typically used to treat depression. For example, doxepin (Silenor) is a TCA that due to its side effect of sedation is often used to treat insomnia. (Ref 3, 4 and 6)
Second- and Third-generation Histamine H1-receptor Blockers
The second-generation of H1-receptor antagonists were developed in order to avoid the drowsy effects of the first class. These antihistamines have the same actions as the first-generation but are known for less daytime drowsiness, dry mouth, and confusion. Used to treat daytime seasonal allergy symptoms, members of this class are loratidine (Claritin), cetirizine (Zyrtec), and the eye drops olopatadine ophthalmic (Pataday). According to an article published in the "Journal of Allergy and Clinical Immunology" in April 2004, the third-generation of H1-blockers have even less effects on the brain then even the second-generation and greater blockage from histamine release from mast cells. This class of drugs are made from the second-generation in forms called metabolites, which is easier for the body to use. Metabolites are by-products of medications that have been broken down by the body in the cells. Some of the medications in this class are levocetirizine (Xyzal) which comes from cetirizine, desloratadine (Clarinex) the metabolite of loratadine, and fexofenadine (Allegra) which was developed from terfenadine which is no longer on the market. (See ref 2,3, 4, 6, 9)
Histamine H2-receptor Blockers
While H1-receptors are in the brain, blood vessels, skin and air passages, H2-receptors are found largely in the stomach lining. Stimulation of H2-receptors signals cells in the stomach walls to secrete gastric acids. H2-blockers were specifically designed to lower the secretion of these acids and help alleviate heartburn symptoms as well as prevent GERD or stomach ulcers from forming. Not having immediate effects, these drugs can take 60 to 90 minutes before they work, and even then symptoms may not begin to resolve for 2 weeks. (Ref 5 and 9). Included in this group are the drugs ranitidine (Zantac), nizatidine (Axid AR), cimetidine (Tagamet), and famotidine (Pepcid AC). (See ref 5 and 9). Side effects of these medications consist of headache, diarrhea, and dizziness. (See ref 5).
Histamine H3-receptor Blockers
H3-receptors are located within the brain and have been found to be associated with wakefulness. Thiaperamide was the first H3-blocker created but was shortly found to be toxic to the liver and became replaced by pitolisant. According to an article published in the "British Journal of Pharmacology" in January 2011, this class of drugs have great potential for use in conditions affecting the sleep-wake cycle such as narcolepsy, a sleep disorder characterized by daytime sudden attacks of sleep, and Parkinson disease which is a progressive degenerative disorder of the brain that affects movement, fatigue, and memory. (See ref 7). These drugs are still being studied in further detail.
Warnings and Precautions
If a woman is breastfeeding or pregnant, she should contact her doctor before taking any of these medications. Caution should be used in people with kidney and liver problems before taking antihistamines. If any symptoms of allergies such as rash, chest pain, swelling of the throat or face, and shortness of breath occur upon taking these medications, a person should contact their healthcare provider immediately.
- Neuropsychopharmacology: The Fifth Generation of Progress; Kenneth L. Davis et al.
- Journal of Allergy and Clinical Immunology: Levocetirizine Better Protects Than Desloratadine in a Nasal Provocation With Allergen
- National Institute of Diabetes and Digestive and Kidney Diseases: LiverTox: Diphenhydramine
- Tulane University School of Medicine: First Generation H1 Blockers
- Medline Plus National Institutes of Health: H2 Blockers
- University of Illinois Chicago: Histamine and Anti-histamine Drugs
- British Journal of Pharmacology: Review- The Histamine H3 Receptor: From Discovery to Clinical Trials With Pitolisant
- Drugs & Medications: H2 blockers
- Indian Journal of Dermatology, Venereology, and Leprology: Histamine 2 Blocker Potentiates the Effects of Histamine 1 Blocker in Suppressing Histamine-induced Wheal