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An antihistamine , also known as a histamine receptor blocker or histamine receptor antagonist , is an active ingredient that weakens or eliminates the effect of the body's own messenger substance histamine by blocking histamine receptors ( antagonism ) or lowering their receptor activity below the basal activity ( inverse agonism ). Antihistamines are divided into H 1 , H 2 , H 3 and H 4 antihistamines according to their selectivity for the four different histamine receptors . Only the H 1 and H 2 antihistamines are used, in particular, for the treatment of allergies or against gastric mucosal inflammation .

The first antihistamines were discovered by Ernest Fourneau , Daniel Bovet and Anne-Marie Staub at the Pasteur Institute in the 1930s ( thymolethyldiethylamine , 1937). In 1939, Staub coined the expression “antihistamines” for the antagonists of anaphylactic or allergic reactions, as these are similar to the effects of histamines. With phenbenzamine ( Antergan ), the first therapeutically used antihistamine was developed in 1942 by Bernard Halpern on the basis of previous development work at the Pasteur Institute near Rhône-Poulenc .

Antihistamines played an important role in the development of the first neuroleptics .

Overdoses can be treated with physostigmine .

H 1 antihistamines

H 1 antihistamines inhibit the histamine effects mediated via H 1 receptors . The most important area of ​​application of the H 1 antihistamines is the treatment of allergic complaints such as reddening of the skin, itching, conjunctivitis and rhinitis . They have different degrees of ability to cross the blood-brain barrier (CNS accessibility), and thus show a different spectrum of additional central nervous effects and side effects . H 1 antihistamines are divided into preparations of the first, second and sometimes third generation, the H 1 antihistamines of the first, on the one hand, and second and third generation, on the other hand, differing mainly in their CNS penetration .

First generation H 1 antihistamines

First generation H 1 antihistamines have been known since the 1930s. Measured in terms of the number of therapeutically used substances, the effect on the H 1 receptor is the pharmacologically most important target, on par with the glucocorticoid receptor . In addition to the inhibitory effect on H 1 receptors, some representatives also have an antagonistic effect on muscarinic receptors (e.g. diphenhydramine ), dopamine receptors (e.g. promethazine ) or serotonin receptors (e.g. promethazine). First generation H 1 antihistamines usually have good CNS accessibility. In this way, they also inhibit the effects of histamine on H 1 receptors in the central nervous system (e.g. vomiting , awakening).

Many of the characteristic side effects of first generation H 1 antihistamines, such as: B. the sedative effect or weight gain are due to the CNS penetrability of the substances and / or their insufficient selectivity. Since newer H 1 antihistamines, which do not cross the blood-brain barrier, are available, H 1 anti-histamines of the first generation are comparatively less important than oral antiallergic drugs. For this they are mainly used externally (ointments, nasal sprays, eye drops). Taking advantage of the central nervous effects, H 1 antihistamines of the first generation are used today in particular as antiemetics for the treatment of motion sickness and as sleep aids . Their low-dose use with analgesics in combination preparations against flu infections is, however, controversial.

Second generation H 1 antihistamines

The H 1 antihistamines of the second generation differ from those of the first generation essentially in that they are poorly or not at all accessible to the CNS. They are therefore considered to be antiallergic agents without any significant sedating properties. Although the aim of the development of the second generation H 1 antihistamines was to create antiallergic drugs with fewer side effects, some representatives ( astemizole and partly in Germany terfenadine ) were dated because of the generation of severe cardiac arrhythmias (caused for example by a QTc time extension ) Market taken. In some cases, taste disorders can occur with individual topical antihistamines .

Third generation H 1 antihistamines

Levocetirizine , desloratadine , fexofenadine and rupatadine are sometimes referred to as third generation H 1 antihistamines as further developments of the second generation H 1 antihistamines. However, these are terms from the field of marketing. They are the active enantiomer of cetirizine (levocetirizine) or the active metabolites of loratadine (desloratadine) and terfenadine (fexofenadine) or further developments as in the case of rupatadine. While the development of fexofenadine was associated with a gain in therapeutic safety compared to terfenadine (reduced risk of cardiac arrhythmias), levocetirizine and desloratadine have hardly any therapeutic advantages over cetirizine and loratadine. Rupatadine also has PAF -antagonistic properties.

H 2 antihistamines

H 2 antihistamines or H₂ receptor antagonists are drugs that inhibit the histamine action mediated by H 2 receptors . H 2 receptors can u. a. in the heart, in the blood vessels and especially in the gastric mucosa , where they are jointly responsible for the production of gastric acid . That is why they are used in the treatment of gastric and duodenal ulcers . They are also used as an adjunct therapy to the long-term use of certain painkillers (e.g. acetylsalicylic acid ) to reduce the occurrence of gastric and duodenal ulcers. For these indications, however, they have become less important than drugs from the group of proton pump inhibitors , which have a more favorable risk-benefit ratio.

The development of H 2 antihistamines began with the discovery of the H 2 receptors and the H 2 receptor antagonist burimamid by James W. Black . Today the H 2 antihistamines cimetidine , famotidine , nizatidine , ranitidine and roxatidine are used therapeutically.

H 3 antihistamines

H 3 antihistamines are drugs that inhibit the effects of histamine on H 3 receptors . Betahistine , which is characterized by a simultaneous agonism at the H 1 receptor and is used for attacks of dizziness, and pitolisant , which is approved for the treatment of narcolepsy, are used therapeutically . Other representatives, such as B. Cipralisant are in clinical testing. H 3 antihistamines are being traded as potential drugs for the treatment of ADHD , narcolepsy and Alzheimer's disease .

H 3 antihistamines: thioperamide , clobenpropit , proxyfan , ciproxyfan

H 4 antihistamines

H 4 antihistamines are substances that inhibit the effects of histamine on the H 4 receptor . Since this receptor was only discovered in 2000, only a few antagonists are available so far (e.g. thioperamide , clobenpropit , JNJ7777120 ). Since this receptor is involved in the chemotaxis of immune and inflammatory cells, H 4 antihistamines are being discussed as potential anti-inflammatory drugs.


Web links

Wiktionary: Antihistamine  - explanations of meanings, word origins, synonyms, translations

Individual evidence

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  2. D. Bovet , A. Staub : Action protectrice des éthers phenoliques au cours l'intoxication histaminique. In: Comptes Rendus des Séances et Mémoires de la Société de Biologie. Volume 124, 1937, pp. 547-549.
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  4. ^ Pharmaceutical newspaper online: Awake through the allergy season (edition 13/2011) .
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  7. Mutschler, Ernst: Mutschler drug effects. Pharmacology, clinical pharmacology, toxicology. 10th edition. Stuttgart. 2013.
  8. Pharmaceutical newspaper of November 20, 2015: Pitolisant: Histamine modulator against narcolepsy . Retrieved May 22, 2017.
  9. a b c d e f Pharmazeutische Zeitung : New generations of antihistamines . Edition 32/2011. Retrieved April 9, 2014.
  10. de Esch IJ, Thurmond RL, Jongejan A. & Leurs R. (2005). The histamine H4 receptor as a new therapeutic target for inflammation. Trends Pharmacol. Sci. , 26 , 462-469.