Histamine antagonist
Antihistamines, and histamine receptor blockers or histamine receptor antagonists are agents which reduce or eliminate by histamine receptors blocking (antagonism ) or its receptor activity even under the basal activity decrease (inverse Agonistmus ) the effect of the endogenous neurotransmitter histamine. Antihistamines are divided according to their selectivity for the four different histamine receptors H1, H2, H3 and H4 antihistamines. Only the H1 and H2 antihistamines currently have a therapeutic significance and in particular for the treatment of allergies and used against gastritis.
The first antihistamines were by Ernest Fourneau, Daniel Bovet and Anne -Marie dust in the 1930s discovered at the Pasteur Institute ( Thymolethyldiethylamin, 1937) With Phenbenzamin ( Antergan ) was the first antihistamine used for therapeutic purposes in 1942 by Bernard Halpern on the basis of previous development work at the Institute Pasteur developed at Rhône -Poulenc.
H1 - antihistamines
H1 - antihistamines inhibit histamine on H1 receptors mediated effects. The most important application of H1 - antihistamines is the treatment of allergic symptoms such as skin redness, itching, conjunctivitis and rhinitis. They have a different strong sense of ability to cross the blood- brain barrier ( CNS marketability ), and thus show a different spectrum of additional central nervous system effects and side effects. H1 - antihistamines are divided into preparations of the first, second and sometimes third generation, which differ H1 antihistamines of the first on the one hand and the second and third generation on the other hand mainly through their central nervous system more easily.
H1 - first-generation antihistamines
H1 - first-generation antihistamines have been known since the 1930s. Based on the number substances used in therapy is the effect on the H1 receptor par with the glucocorticoid receptor, the pharmacologically important target (Target ). In addition to the inhibitory effect on H1 receptors, some representatives also have an antagonistic effect on muscarinic receptors (eg, diphenhydramine), dopamine receptors (eg, promethazine ), or serotonin receptors (eg, promethazine ). H1 - first-generation antihistamines usually have a good CNS of movement. In this way, they also inhibit the effects of histamine at H1 - receptors in the central nervous system ( eg vomiting, awakening ).
Many of the typical side effects of first-generation H1 - antihistamines, such as the sedative effects are due to the movement rate of the central nervous system agents. Because newer H1 antihistamines that do not cross the blood -brain barrier, are available, H1 - antihistamines have the first generation of comparatively little importance as an oral antiallergic agents. For this, they are primarily used externally ( ointments, nasal sprays, eye drops ). Taking advantage of the central nervous system effects, see H1 - antihistamines first generation today especially as antiemetics for the treatment of motion sickness and as a sleep aid application. Your application with low-dose analgesics in combination treatments for the common cold is controversial.
- Ethylenediamines: mepyramine ( pyrilamine ), tripelennamine ( Pyribenzamin ) antazoline, dimetindene, ( bamipine )
- Ethanolamine: diphenhydramine, carbinoxamine, doxylamine, clemastine
- Alkylamines: pheniramine, chlorphenamine ( chlorpheniramine ), Dexchlorphenamin, brompheniramine, triprolidine
- Piperazines: hydroxyzine, meclizine, cyclizine
- Tricyclic antihistamines: promethazine, alimemazine ( trimeprazine ), cyproheptadine, azatadine, latrepirdine
H1 - antihistamines of the second generation
The H1 second-generation antihistamines differ from those of the first generation mainly due to lack of poorer CNS of movement. Therefore, you are considered anti-allergic agents without significant sedative properties. Although the goal of the development of the H1 antihistamines of the second generation was to create anti-allergic agents with fewer side effects, had some representatives ( astemizole and terfenadine ( in Germany still partially allowed) ) be withdrawn from the market due to the generation of severe cardiac arrhythmia.
- For systemic use: acrivastine, astemizole, cetirizine, ebastine, loratadine, Mizolastine, terfenadine, rupatadine
- For the topical ( local ) application: azelastine, levocabastine, olopatadine, epinastine
H1 - antihistamines third generation
Further developments in the H1 - second-generation antihistamines, levocetirizine, desloratadine, fexofenadine and rupatadine are sometimes referred to as H1 - antihistamines of the third generation. However, the names are always in the field of marketing. They are the active enantiomer of cetirizine ( levocetirizine ) or the active metabolite of loratadine ( desloratadine ) and terfenadine ( fexofenadine ) and further development, as in the case of rupatadine. During the development of fexofenadine was associated with a gain in therapeutic safety ( no heart rhythm disorders ), levocetirizine and desloratadine compared with cetirizine and loratadine have little therapeutic benefits. Rupatadine has PAF- antagonistic properties.
H2 antihistamines
H2 - antihistamines or H ₂ - receptor antagonists are drugs which inhibit histamine mediated through H2-receptors effect. H2 receptors can be detected where they are responsible for the production of stomach acid, inter alia, in the heart, blood vessels, and in particular in the gastric mucosa. Therefore, they are used in the therapy of gastric and duodenal ulcers. They are also used as adjunctive therapy in the long-term use of certain pain medications (such as aspirin ) to reduce the incidence of gastric and duodenal ulcers. For these indications, but they have to drugs from the group of proton pump inhibitors, which have a more favorable risk-benefit ratio declined in importance.
The evolution of H2 antihistamines began with the discovery of H2- receptors and the H2 - receptor antagonists burimamide by James W. Black. Today, the H2 antihistamines cimetidine, famotidine, nizatidine, ranitidine and roxatidine find therapeutic application.
H3 antihistamines
H3 Antihistamines are drugs which inhibit the effects of histamine on H3 receptors. A therapeutic use is currently taking betahistine, which is characterized by a simultaneous agonism at the H1 receptor and is used for dizziness. Other representatives, such as Cipralisant, are in clinical trials. H3 antihistamines are traded as potential drugs for the treatment of ADHD, narcolepsy and Alzheimer 's disease.
H3 antihistamines: thioperamide, clobenpropit, Proxyfan, Ciproxyfan
H4 antihistamines
H4 - Antihistamines are substances that inhibit the effects of histamine on the H4 receptor. Since this receptor was only discovered in 2000, are only a few antagonists are available ( eg thioperamide, JNJ7777120 ). Since this receptor is involved in the chemotaxis of immune and inflammatory cells, H4 - antihistamines are discussed as potential anti-inflammatory drugs.