H1-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 both block the binding of histamine, and reduce its constitutive activity, an effect which is opposite to histamine's. Most<unk> s are inverse agonists at the H1 receptor, but it was previously thought that they were antagonists. 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, may therefore be 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. A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation<unk> s having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent with non-opioid ones as well. The most common<unk> s utilized for this purpose include hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example. Second-generation<unk> s cross the blood–brain barrier to a much lesser extent than the first-generation<unk> s. They minimize sedatory effects due to their focused effect on peripheral histamine receptors. However, upon high doses second-generation<unk> s will begin to act on the central nervous system and thus can induce drowsiness when ingested in higher quantity. Additionally, some second-generation<unk> s, notably cetirizine, can interact with CNS psychoactive drugs such as bupropion and benzodiazepines. H1 antagonists/inverse agonists *Acrivastine *Alimemazine (a phenothiazine used as antipruritic, antiemetic and sedative) *Amitriptyline (tricyclic antidepressant) *Amoxapine (tetracyclic antidepressant) *Azelastine *Bilastine *Bromodiphenhydramine *Brompheniramine *Buclizine *Carbinoxamine *Cetirizine (Zyrtec) *Chlorodiphenhydramine *Chlorpheniramine *Chlorpromazine (low-potency typical antipsychotic, also used as an antiemetic) *Chlorprothixene (low-potency typical antipsychotic, trade name: Truxal) *Chloropyramine (first generation<unk>  marketed in Eastern Europe) *Cinnarizine (also used for motion sickness and vertigo) *Clemastine *Clomipramine (tricyclic antidepressant) *Clozapine (atypical antipsychotic; trade name: Clozaril) *Cyclizine *Cyproheptadine *Desloratadine *Dexbrompheniramine *Dexchlorpheniramine *Dimenhydrinate (used as an antiemetic and for motion sickness) *Dimetindene *Diphenhydramine (Benadryl) *Dosulepin (tricyclic antidepressant) *Doxepin (tricyclic antidepressant) *Doxylamine (most commonly used as an over-the-counter drug sedative) *Ebastine *Embramine *Fexofenadine (Allegra/Telfast) *Hydroxyzine (also used as an anxiolytic and for motion sickness; trade names: Atarax, Vistaril) *Imipramine (tricyclic antidepressant) *Levocabastine (Livostin/Livocab) *Levocetirizine (Xyzal) *Levomepromazine (low-potency typical antipsychotic) *Loratadine (Claritin) *Maprotiline (tetracyclic antidepressant) *Meclizine (most commonly used as an antiemetic) *Mianserin (tetracyclic antidepressant) *Mirtazapine (tetracyclic antidepressant, also has antiemetic and appetite-stimulating effects; trade name: Remeron) *Olanzapine (atypical antipsychotic; trade name: Zyprexa) *Olopatadine (used locally) *Orphenadrine (a close relative of diphenhydramine used mainly as a skeletal muscle relaxant and anti-Parkinsons agent) *Periciazine (low-potency typical antipsychotic) *Phenindamine *Pheniramine *Phenyltoloxamine *Promethazine (Phenergan) *Pyrilamine (crosses the blood–brain barrier; produces drowsiness) *Quetiapine (atypical antipsychotic; trade name: Seroquel) *Rupatadine (Alergoliber) *Trazodone (SARI antidepressant/anxiolytic/hypnotic with mild H1 blockade action) *Tripelennamine *Triprolidine H2-antihistamines H2-antihistamines, like H1-antihistamines, exist as inverse agonists and neutral antagonists. They act on H2 histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H2 to stimulate acid secretion; drugs that inhibit H2 signaling thus reduce the secretion of gastric acid. H2-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses. Examples include: *Cimetidine *Famotidine *Lafutidine *Nizatidine *Ranitidine *Roxatidine *Tiotidine H3-antihistamines An H3-antihistamine is a classification of drugs used to inhibit the action of histamine at the H3 receptor. H3 receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H1 receptors in the cerebral cortex. Consequently, unlike the H1-antihistamines which are sedating, H3-antihistamines have stimulant and cognition-modulating effects. Examples of selective H3-antihistamines include: *Clobenpropit *ABT-239 *Ciproxifan *Conessine *A-349,821. * Thioperamide H4-antihistamines H4-antihistamines inhibit the activity of the H4 receptor. Examples: * Thioperamide * JNJ 7777120 * VUF-6002
Antihistamine
Antileukotriene
Aeroallergen
Depressogen
Anticorticosteroid
Allergen
Opioid
Querulant