A histamine antagonist (commonly called an antihistamine) is a pharmaceutical drug that inhibits the action of histamine by blocking it from attaching to histamine receptors; or it may inhibit the enzymatic activity of histidine decarboxylase, catalyzing the transformation of histidine into histamine (atypical antihistaminics).
Antihistamines are commonly used for the relief of allergies caused by intolerance of proteins.[1]
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Contents
- 1 Clinical effects
- 2 Clinical: H1- and H2-receptor antagonists
- 2.1 H1-receptor antagonists
- 2.2 H2-receptor antagonists
- 3 Experimental: H3- and H4-receptor antagonists
- 3.1 H3-receptor antagonists
- 3.2 H4-receptor antagonists
- 4 Others
- 4.1 Atypical antihistaminics
- 4.2 Mast cell stabilizers
- 4.3 Other agents with antihistaminergic activity
- 5 References
- 6 External links
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Clinical effects
Histamines produce increased vascular permeability, causing fluid to escape from capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and watery eyes. Histamine also promotes angiogenesis.
Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells. They exert a competitive antagonism to histamines.
Itching and sneezing are suppressed by antihistamine blocking of H1-receptors on nasal sensory nerves.[2]
Clinical: H1- and H2-receptor antagonists
H1-receptor antagonists
Main article: H1 antagonist
In common use, the term antihistamine refers only to H1 antagonists, also known as H1 antihistamines. It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se.[3] Clinically, H1 antagonists are used to treat allergic reactions. Sedation is a common side-effect, and some H1 antagonists, such as diphenhydramine and doxylamine, are also used to treat insomnia. However, second-generation antihistamines do not cross the blood–brain barrier, and as such do not cause drowsiness.
Examples:
- Azelastine
- Brompheniramine
- Buclizine
- Bromodiphenhydramine
- Carbinoxamine
- Cetirizine
- Chlorpromazine (antipsychotic)
- Cyclizine
- Chlorpheniramine
- Chlorodiphenhydramine
- Clemastine
- Cyproheptadine
- Desloratadine
- Dexbrompheniramine
- Deschlorpheniramine
- Dexchlorpheniramine
- Dimenhydrinate (most commonly used as an antiemetic)
- Dimetindene
- Diphenhydramine (Benadryl)
- Doxylamine (most commonly used as an OTC sedative)
- Ebastine
- Embramine
- Fexofenadine
- Levocetirizine
- Loratadine
- Meclozine (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)
- Phenindamine
- Pheniramine
- Phenyltoloxamine
- Promethazine
- Pyrilamine
- Quetiapine (antipsychotic)
- Rupatadine
- Tripelennamine
- Triprolidine
H2-receptor antagonists
Main article: H2 antagonist
H2 antagonists, like H1 antagonists, are also inverse agonists and not true antagonists. H2 histamine receptors, found principally in the parietal cells of the gastric mucosa, are used to reduce the secretion of gastric acid, treating gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease.
Examples:
- Cimetidine
- Famotidine
- Lafutidine
- Nizatidine
- Ranitidine
- Roxatidine
Experimental: H3- and H4-receptor antagonists
These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H3-antagonists have a stimulant and nootropic effect, and are being investigated for the treatment of conditions such as ADHD, Alzheimer's disease, and schizophrenia, whereas H4-antagonists appear to have an immunomodulatory role and are being investigated as anti-inflammatory and analgesic drugs.
H3-receptor antagonists
Main article: H3 antagonist
Examples:
- A-349,821
- ABT-239
- Ciproxifan
- Clobenpropit
- Conessine
- Thioperamide
H4-receptor antagonists
Examples:
- Thioperamide
- JNJ 7777120
- VUF-6002
Others
Atypical antihistaminics
They inhibit the enzymatic activity of histidine decarboxylase :
Mast cell stabilizers
Main article: Mast cell stabilizer
Mast cell stabilizers appear to stabilize the mast cells to prevent degranulation and mediator release. These drugs are not usually classified as histamine antagonists, but have similar indications.
Examples:
- Cromoglicate (cromolyn)
- Nedocromil
- Beta 2 (β2) adrenergic agonists
Other agents with antihistaminergic activity
Many drugs used for other indications possess unwanted antihistaminergic activity.[citation needed]
References
- ^ Sicherer, Scott H. M.D., Understanding and Managing Your Child's Food Allergy. Baltimore: The Johns Hopkins University Press, 2006 ISBN 0-8018-8492-6.
- ^ Monroe, EW; Daly, AF; Shalhoub, RF (1997). "Appraisal of the validity of histmine-induced wheal and flare is used to predict the clinical efficacy of antihistamines". The Journal of allergy and clinical immunology 99 (2): S798–806. PMID 9042073.
- ^ Leurs R, Church MK, Taglialatela M (2002). "H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects". Clin Exp Allergy 32 (4): 489–98. doi:10.1046/j.0954-7894.2002.01314.x. PMID 11972592.
External links
- Histamine+antagonist at the US National Library of Medicine Medical Subject Headings (MeSH)
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Antihistamines (R06)
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| Aminoalkyl ethers |
- Bromazine/Bromodiphenhydramine
- Carbinoxamine
- Clemastine
- Chlorphenoxamine
- Diphenylpyraline
- Diphenhydramine
- Doxylamine
- Orphenadrine
- Phenyltoloxamine
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| Substituted alkylamines |
- Brompheniramine
- Chlorphenamine
- Dexbrompheniramine
- Dexchlorpheniramine
- Dimetindene
- Pheniramine
- Talastine
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| Substituted ethylenediamines |
- Chloropyramine
- Histapyrrodine
- Mepyramine
- Methapyrilene
- Tripelennamine (Pyribenzamine)
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| Phenothiazine derivatives |
- Alimemazine
- Hydroxyethylpromethazine
- Isothipendyl
- Mequitazine
- Methdilazine
- Oxomemazine
- Promethazine
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| Piperazine derivatives |
- Buclizine
- Cetirizine
- Chlorcyclizine
- Cinnarizine
- Cyclizine
- Hydroxyzine
- Levocetirizine
- Meclizine
- Niaprazine
- Oxatomide
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| Others for systemic use |
- Antazoline
- Azatadine
- Bamipine
- Cyproheptadine
- Deptropine
- Dimebon
- Ebastine
- Epinastine
- Ketotifen
- Mebhydrolin
- Mizolastine
- Phenindamine
- Pimethixene
- Pyrrobutamine
- Rupatadine
- Triprolidine
- selective (Acrivastine
- Astemizole
- Azelastine
- Desloratadine
- Fexofenadine
- Loratadine
- Terfenadine)
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| For topical use |
- Bamipine
- Chloropyramine
- Chlorphenoxamine
- Clemastine
- Dimetindene
- Diphenhydramine
- Isothipendyl
- Mepyramine
- Promethazine
- Thenalidine
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| Antiallergic agents excluding corticosteroids |
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| Other antiallergics |
- Emedastine
- Epinastine
- Ketotifen
- Montelukast
- Olopatadine
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Histaminergics
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| Receptor |
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H1
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- Agonists: 2-Pyridylethylamine
- Betahistine
- Histamine
- HTMT
- UR-AK49
Antagonists: 1st generation: 4-Methyldiphenhydramine
- Alimemazine
- Antazoline
- Azatadine
- Bamipine
- Benzatropine/Benztropine
- Bepotastine
- Bromazine
- Brompheniramine
- Buclizine
- Captodiame
- Carbinoxamine
- Chlorcyclizine
- Chloropyramine
- Chlorothen
- Chlorphenamine
- Chlorphenoxamine
- Cinnarizine
- Clemastine
- Clobenzepam
- Clocinizine
- Cyclizine
- Cyproheptadine
- Dacemazine
- Deptropine
- Dexbrompheniramine
- Dexchlorpheniramine
- Dimenhydrinate
- Dimetindene
- Diphenhydramine
- Diphenylpyraline
- Doxylamine
- Embramine
- Etodroxizine
- Etybenzatropine/Ethylbenztropine
- Etymemazine
- Flunarizine
- Histapyrrodine
- Homochlorcyclizine
- Hydroxyethylpromethazine
- Hydroxyzine
- Isopromethazine
- Isothipendyl
- Meclozine
- Mepyramine/Pyrilamine
- Mequitazine
- Methafurylene
- Methapyrilene
- Methdilazine
- Moxastine
- Niaprazine
- Orphenadrine
- Oxatomide
- Oxomemazine
- Phenindamine
- Pheniramine
- Phenyltoloxamine
- Pimethixene
- Piperoxan
- Pipoxizine
- Promethazine
- Propiomazine
- Pyrrobutamine
- Talastine
- Thenalidine
- Thenyldiamine
- Thiazinamium
- Thonzylamine
- Tolpropamine
- Tripelennamine
- Triprolidine
- 2nd generation: Acrivastine
- Alinastine
- Astemizole
- Azelastine
- Bamirastine
- Barmastine
- Bepiastine
- Bepotastine
- Bilastine
- Cabastinen
- Carebastine
- Cetirizine
- Clemastine
- Clemizole
- Clobenztropine
- Dorastine
- Ebastine
- Emedastine
- Epinastine
- Flezelastine
- Ketotifen
- Latrepirdine
- Levocabastine
- Linetastine
- Loratadine
- Mapinastine
- Mebhydrolin
- Mizolastine
- Moxastine
- Noberastine
- Octastine
- Olopatadine
- Perastine
- Piclopastine
- Rocastine
- Rupatadine
- Setastine
- Talastine
- Temelastine
- Terfenadine
- Zepastine
- 3rd generation: Desloratadine
- Fexofenadine
- Levocetirizine
- Ungrouped: Belarizine
- Efletirizine
- Elbanizine
- Flotrenizine
- Medrylamine
- Napactadine
- Pibaxizine
- Tagorizine
- Trelnarizine
- Trenizine
- Vapitadine
- Miscellaneous: Tricyclic antidepressants (amitriptyline,
- doxepin,
- trimipramine, etc)
- Tetracyclic antidepressants (mianserin,
- mirtazapine, etc)
- Typical antipsychotics (chlorpromazine,
- thioridazine, etc)
- Atypical antipsychotics (clozapine,
- olanzapine,
- quetiapine, etc)
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H2
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- Agonists: Amthamine
- Betazole
- Dimaprit
- Histamine
- HTMT
- Impromidine
- UR-AK49
Antagonists: Bisfentidine
- Burimamide
- Cimetidine
- Dalcotidine
- Donetidine
- Ebrotidine
- Etintidine
- Famotidine
- Lafutidine
- Lamtidine
- Lavoltidine/Loxtidine
- Lupitidine
- Metiamide
- Mifentidine
- Niperotidine
- Nizatidine
- Osutidine
- Oxmetidine
- Pibutidine
- Quisultazine/Quisultidine
- Ramixotidine
- Ranitidine
- Roxatidine
- Sufotidine
- Tiotidine
- Tuvatidine
- Venritidine
- Xaltidine
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H3
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- Agonists: α-Methylhistamine
- Cipralisant
- Histamine
- Imetit
- Immepip
- Immethridine
- Methimepip
- Proxyfan
Antagonists: A-349,821
- A-423,579
- ABT-239
- Betahistine
- Burimamide
- Ciproxifan
- Clobenpropit
- Conessine
- GSK-189,254
- Impentamine
- Iodophenpropit
- JNJ-5,207,852
- MK-0249
- NNC-38-1,049
- PF-03654746
- Pitolisant
- SCH-79,687
- Thioperamide
- VUF-5,681
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H4
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- Agonists: 4-Methylhistamine
- Histamine
- VUF-8,430
Antagonists: JNJ-7,777,120
- Thioperamide
- VUF-6,002
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| Transporter |
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VMAT
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- Inhibitors: Ibogaine
- Reserpine
- Tetrabenazine
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| Enzyme |
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HDC
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- Inhibitors: Catechin
- Meciadanol
- Naringenin
- Tritoqualine
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DAO
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- Inhibitors: Aminoguanidine
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| Others |
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Endogenous
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- Histamine; Precursors: L-Histidine; Cofactors: Vitamin B6
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Neuromodulation
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| Types |
- ♦ Enzyme: Inducer
- Inhibitor
- ♦ Ion channel: Opener
- Blocker
- ♦ Receptor: Agonist
- Antagonist
- Positive allosteric modulator (PAM)
- Negative allosteric modulator (NAM)
- Inverse agonist
- ♦ Transporter [Reuptake]: Enhancer (RE)
- Inhibitor (RI)
- Releaser (RA)
- ♦ Miscellaneous: Precursor
- Cofactor
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| Classes |
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Enzyme
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see Enzyme inhibition
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Ion channel
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- Calcium channel blocker (CCB)
- Potassium channel blocker (PCB)
- Sodium channel blocker (SCB)
- Potassium channel opener (PCO)
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Receptor &
transporter
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BA/M
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Adrenergic
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- Adrenergic receptor agonist (α
- β (1
- 2))
- Adrenergic receptor antagonist (α (1
- 2), β)
- Adrenergic reuptake inhibitor (ARI)
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Dopaminergic
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- Dopamine receptor agonist
- Dopamine receptor antagonist
- Dopamine reuptake inhibitor (DRI)
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Histaminergic
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- Histamine receptor agonist
- Histamine receptor antagonist (H1
- H2
- H3)
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Serotonergic
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- Serotonin receptor agonist
- Serotonin Receptor Antagonist (5-HT3)
- Serotonin reuptake inhibitor (SRI)
- Serotonin reuptake enhancer (SRE)
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AA
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GABAergic
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- GABA receptor agonist
- GABA receptor antagonist
- GABA reuptake inhibitor (GRI)
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Glutamatergic
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- Glutamate receptor agonist (AMPA)
- Glutamate receptor antagonist (NMDA)
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Cholinergic
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- Acetylcholine receptor agonist (Muscarinic
- Nicotinic)
- Acetylcholine receptor antagonist (Muscarinic
- Nicotinic (Ganglionic
- Muscular))
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Endocannabinoid
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- Cannabinoid receptor agonist
- Cannabinoid receptor antagonist
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Opioid
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- Opioid receptor agonist
- Opioid receptor antagonist
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Other
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- Adenosine reuptake inhibitor (AdoRI)
- Angiotensin II receptor antagonist
- Endothelin receptor antagonist
- NK1 receptor antagonist
- Vasopressin receptor antagonist
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Miscellaneous
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- Cofactor (see Enzyme cofactors)
- Precursor (see Amino acids)
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