Antihistamines are

drugs A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestio ...

which treat

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a type I hypersensitivity reaction. Signs a ...

common cold The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...

influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...

, and other

allergies Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides relief from

nasal congestion Nasal congestion is the partial or complete blockage of nasal passages, leading to impaired nasal breathing, usually due to membranes lining the nose becoming swollen from inflammation of blood vessels. Background In about 85% of cases, nasal ...

sneezing A sneeze (also known as sternutation) is a semi-autonomous, convulsive expulsion of air from the lungs through the nose and mouth, usually caused by foreign particles irritating the nasal mucosa. A sneeze expels air forcibly from the mouth a ...

, or

hives Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...

caused by

pollen Pollen is a powdery substance produced by most types of flowers of seed plants for the purpose of sexual reproduction. It consists of pollen grains (highly reduced Gametophyte#Heterospory, microgametophytes), which produce male gametes (sperm ...

, dust mites, or

animal allergy In medicine, animal allergy is hypersensitivity to certain substances produced by animals, such as the proteins in animal hair and saliva. It is a common type of allergy. Signs and symptoms Symptoms of an allergic reaction to animals may include i ...

with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

sinusitis Sinusitis, also known as rhinosinusitis, is an inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include production of thick nasal mucus, nasal congestion, facial congestion, facial pain, facial pressure ...

, and

lower respiratory tract infection Lower respiratory tract infection (LRTI) is a term often used as a synonym for pneumonia but can also be applied to other types of infection including lung abscess and acute bronchitis. Symptoms include shortness of breath, weakness, fever, cou ...

. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use. Although the general public typically uses the word "antihistamine" to describe drugs for treating allergies, physicians and scientists use the term to describe a class of drug that opposes the activity of

histamine receptor The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand. Histamine is a neurotransmitter involved in various physiological processes. There are four main types of histamine recep ...

s in the body. In this sense of the word, antihistamines are subclassified according to the

histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...

receptor that they act upon. The two largest classes of antihistamines are H₁-antihistamines and H₂-antihistamines. H₁-antihistamines work by binding to histamine H₁ receptors in

mast cells A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a ...

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

, and

endothelium The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...

in the body as well as in the tuberomammillary nucleus in the brain. Antihistamines that target the histamine H₁-receptor are used to treat allergic reactions in the nose (e.g., itching, runny nose, and sneezing). In addition, they may be used to treat

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, motion sickness, or

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

caused by problems with the

inner ear The inner ear (internal ear, auris interna) is the innermost part of the vertebrate ear. In vertebrates, the inner ear is mainly responsible for sound detection and balance. In mammals, it consists of the bony labyrinth, a hollow cavity in the ...

. H₂-antihistamines bind to histamine H₂ receptors in the upper

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

, primarily in the

stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

. Antihistamines that target the histamine H₂-receptor are used to treat

gastric acid Gastric acid or stomach acid is the acidic component – hydrochloric acid – of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other a ...

conditions (e.g.,

peptic ulcers Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

and acid reflux). Other antihistamines also target H₃ receptors and H₄ receptors.

Histamine receptor The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand. Histamine is a neurotransmitter involved in various physiological processes. There are four main types of histamine recep ...

s exhibit constitutive activity, so antihistamines can function as either a neutral

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

or an

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

at histamine receptors. Only a few currently marketed H₁-antihistamines are known to function as antagonists.

Medical uses

Histamine makes blood vessels more permeable (

vascular permeability Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the permeability of a blood vessel wall–in other words, the blood vessel wall's capacity to allow for the flow of small molecules ( ...

), causing fluid to escape from

capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...

into tissues, which leads to the classic

symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s of an

allergic reaction Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

—a runny nose and watery eyes. Histamine also promotes

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and ...

. Antihistamines suppress the histamine-induced

wheal response A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, Nail (anatomy), nails, and related muscle and glands. The major funct ...

(swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the Electrochemistry, electrochemical nerv ...

vascular smooth muscle Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood v ...

, glandular cells,

, and

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a p ...

s. Antihistamines can also help correct Eustachian Tube dysfunction, thereby helping correct problems such as muffled hearing, fullness in the ear and even

tinnitus Tinnitus is a condition when a person hears a ringing sound or a different variety of sound when no corresponding external sound is present and other people cannot hear it. Nearly everyone experiences faint "normal tinnitus" in a completely ...

Itch An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

ing,

, and inflammatory responses are suppressed by antihistamines that act on H1-receptors. In 2014, antihistamines such as

desloratadine Desloratadine sold under the brand name Aerius among others, is a tricyclic H1 antagonist, H1 inverse agonist that is used to treat allergy, allergies. It is an active metabolite of loratadine. It was patented in 1984 and came into medical u ...

were found to be effective to complement standardized treatment of

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

due to their

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

properties and their ability to suppress

sebum A sebaceous gland or oil gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur ...

production.

Types

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

s or

s. 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 antihistamines are inverse agonists at the H₁ receptor, but it was previously thought that they were antagonists. Clinically, H₁-antihistamines are used to treat

allergic Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

reactions and

-related disorders.

Sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

is a common side effect of H₁-antihistamines that readily cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

, as they antagonize central histamine receptors involved in wakefulness—blocking histamine signaling in the brain—; some of these drugs, such as

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

and doxylamine, may therefore be used to treat

. H₁-antihistamines can also reduce inflammation, since the expression of

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...

, the transcription factor the regulates inflammatory processes, is promoted by both the receptor's constitutive activity and agonist (i.e.,

) binding at the H₁ receptor. A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation antihistamines having analgesic-sparing (potentiating) effects on

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

analgesics An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

and to some extent with non-opioid ones as well. The most common antihistamines utilized for this purpose include hydroxyzine,

promethazine Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold a ...

(enzyme induction especially helps with

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

and similar

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

opioids), phenyltoloxamine,

orphenadrine Orphenadrine (sold under many brand names) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in ...

, and tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.

Second-generation antihistamine H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of his ...

s cross the

to a much lesser extent than the first-generation antihistamines. They minimize sedatory effects due to their focused effect on peripheral histamine receptors. However, upon high doses second-generation antihistamines will begin to act on the central nervous system and thus can induce drowsiness when ingested in higher quantity.

List of H₁ antagonists/inverse agonists

Acrivastine Acrivastine is a medication used for the treatment of allergies and hay fever. It is a second-generation H1-receptor antagonist antihistamine (like its base molecule triprolidine) and works by blocking histamine H1 receptors. This non-sedating ...

* Alimemazine (a phenothiazine used as

antipruritic Antipruritics, abirritants, or anti-itch drugs, are medications that inhibit itching (Latin: ''pruritus''). Itching is often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, Fungal infection in animals, fungal infections ...

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may ...

and

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

) *

Amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headac ...

(

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

) *

Amoxapine Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylation, demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximat ...

(

) *

Aripiprazole Aripiprazole, sold under the brand name Abilify, among others, is an atypical antipsychotic primarily used in the treatment of schizophrenia, bipolar disorder, and irritability associated with autism spectrum disorder; other uses include as ...

(

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...

, trade name: Abilify) * Brexpiprazole (

, trade name: Rexulti) * Azelastine * Bilastine * Bromodiphenhydramine (Bromazine) * Brompheniramine * Buclizine * Carbinoxamine *

Cetirizine Cetirizine is a second-generation antihistamine, second-generation Peripherally selective antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty ...

(Zyrtec) * Chlophedianol (Clofedanol) * Chlorodiphenhydramine *

Chlorpheniramine Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken orally (by mouth). The medication takes effect within two hour ...

Chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

(low-potency

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics m ...

, also used as an

) *

Chlorprothixene Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group. Medical uses Chlorprothixene's principal indications are the treatment of psychotic disorders (e.g. schizophrenia) and of acut ...

(low-potency

, trade name: Truxal) * Chloropyramine (first generation antihistamine marketed in

Eastern Europe Eastern Europe is a subregion of the Europe, European continent. As a largely ambiguous term, it has a wide range of geopolitical, geographical, ethnic, cultural and socio-economic connotations. Its eastern boundary is marked by the Ural Mountain ...

) * Cinnarizine (also used for

motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include ...

and

) * Clemastine *

Clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyper ...

(

) *

Clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

(

; trade name: Clozaril) * Cyclizine *

Cyproheptadine Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine, first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties. It was patented in 1959 a ...

Desloratadine Desloratadine sold under the brand name Aerius among others, is a tricyclic H1 antagonist, H1 inverse agonist that is used to treat allergy, allergies. It is an active metabolite of loratadine. It was patented in 1984 and came into medical u ...

* Dexbrompheniramine * Dexchlorpheniramine *

Dimenhydrinate Dimenhydrinate, also known as diphenhydramine/8-chlorotheophylline salt and sold under the brand names Dramamine and Gravol, among others, is an over-the-counter medication used to treat motion sickness and nausea. Dimenhydrinate is a theocl ...

(used as an

and for

) * Dimetindene *

Diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

(Benadryl) * Dosulepin (

) * Doxepin (

) * Doxylamine (most commonly used as an

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

) * Ebastine * Embramine *

Fexofenadine Fexofenadine, sold under the brand name Allegra among others, is an antihistamine medication used in the treatment of allergy symptoms such as allergic rhinitis and urticaria. Therapeutically, fexofenadine is a selective peripheral H1 blocke ...

(Allegra/Telfast) *

Fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

* Hydroxyzine (also used as an

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

and for

; trade names: Atarax, Vistaril) *

Imipramine Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. Imipramine is taken by mouth. Common s ...

(

) *

Ketotifen Ketotifen is an antihistamine medication and a mast cell stabilizer used to treat allergic conditions such as conjunctivitis, asthma, and urticaria (hives). Ketotifen is available in ophthalmic (eye drops or drug-eluting contact lenses) and o ...

* Levocabastine (Livostin/Livocab) * Levocetirizine (Xyzal) *

Levomepromazine Levomepromazine, also known as methotrimeprazine, is a phenothiazine neuroleptic drug. Brand names include Nozinan, Levoprome, Detenler, Hirnamin, Levotomin and Neurocil. It is a low-potency antipsychotic (approximately half as potent as chlorp ...

(low-potency

) *

Loratadine Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in drug combinations such as loratadine/pseudoephedrine, in whic ...

(Claritin) * Maprotiline (

tetracyclic antidepressant Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their tetracyclic chemical structure, containing four cyclic compound, rings of atoms, and are closely related to th ...

) * Meclizine (most commonly used as an antiemetic) * Mianserin (

) *

Mirtazapine Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...

(

, also has antiemetic and appetite-stimulating effects; trade name: Remeron) *

Olanzapine Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomitin ...

(

; trade name: Zyprexa) *

Olopatadine Olopatadine, sold under the brand name Patanol among others, is an antihistamine medication used to decrease the symptoms of allergic conjunctivitis and allergic rhinitis (hay fever). It is used as eye drops or as a nasal spray. The eye drops ...

(used locally) *

Orphenadrine Orphenadrine (sold under many brand names) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in ...

(a close relative of diphenhydramine used mainly as a skeletal muscle relaxant and anti-Parkinsons agent) *

Periciazine Periciazine ( INN), also known as pericyazine ( BAN) or propericiazine, is a drug that belongs to the phenothiazine class of typical antipsychotics. Periciazine is not approved for sale in the United States. It is commonly sold in Canada, Ital ...

(low-potency

) * Phenindamine * Pheniramine * Phenyltoloxamine *

Promethazine Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold a ...

(Phenergan) * Pyrilamine (crosses the blood–brain barrier; produces drowsiness) * Quetiapine (

; trade name: Seroquel) * Rupatadine (Alergoliber) * Setastine (Loderix) * Setiptiline (or teciptiline, a

, trade name: Tecipul) *

Trazodone Trazodone is an antidepressant medication used to treat major depressive disorder, anxiety disorders, and insomnia. It is a phenylpiperazine compound of the serotonin antagonist and reuptake inhibitor (SARI) class. The medication is taken or ...

(SARI antidepressant/anxiolytic/hypnotic with mild H₁ blockade action) * Tripelennamine * Triprolidine

H₂-antihistamines

H₂-antihistamines, like H₁-antihistamines, exist as

s and neutral

antagonists An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.H₂ histamine receptors found mainly in the

parietal cell Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions o ...

s of the gastric mucosa, which are part of the endogenous signaling pathway for

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 ulcer Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

s and

gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or ...

. 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 Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. With the development of proton pump ...

Famotidine Famotidine, sold under the brand name Pepcid among others, is a histamine H2 receptor antagonist medication that decreases stomach acid production. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–E ...

* Lafutidine *

Nizatidine Nizatidine is a histamine H2 receptor antagonist that inhibits stomach acid production, and is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease. It was patented in 1980 and approved for medical use in ...

Ranitidine Ranitidine, previously sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It was commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellis ...

Roxatidine Roxatidine acetate is a specific and competitive histamine H2 receptor antagonist drug that is used to treat gastric ulcers, Zollinger–Ellison syndrome, erosive esophagitis, gastro-oesophageal reflux disease, and gastritis.BioSpectrum Bu ...

* Tiotidine

H₃-antihistamines

An H₃-antihistamine is a classification of

used to inhibit the action of

at the H₃ receptor. H₃ receptors are primarily found in the brain and are inhibitory

autoreceptor An autoreceptor is a type of Receptor (biochemistry), receptor located in the cell membrane, membranes of neuron, nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or ...

s located on histaminergic nerve terminals, which modulate the release of

. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

and

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

via stimulation of H₁ receptors in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

. Consequently, unlike the H₁-antihistamines which are sedating, H₃-antihistamines have

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

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 include: * Thioperamide * JNJ 7777120 * VUF-6002

Atypical antihistamines

Histidine decarboxylase inhibitors

Inhibit the action of

histidine decarboxylase The enzyme histidine decarboxylase (, HDC) is transcribed on chromosome 15, region q21.1-21.2, and Catalysis, catalyzes the decarboxylation of histidine to form histamine. In mammals, histamine is an important biogenic amine with regulatory roles ...

: * Tritoqualine *

Catechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from ''catechu'', which is the tannic ...

Mast cell stabilizers

Mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a p ...

stabilizers are drugs which prevent mast cell degranulation. Examples include: * Cromolyn sodium *

Nedocromil Nedocromil sodium is a medication considered a mast cell stabilizer which acts to prevent wheezing, shortness of breath, and other breathing problems caused by asthma. It is administered by an inhaler under the brand name Tilade, and as an eye dr ...

* β-agonists

History

The first H₁ receptor antagonists were discovered in the 1930s and were marketed in the 1940s. Piperoxan was discovered in 1933 and was the first compound with antihistamine effects to be identified. Piperoxan and its analogues were too

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

to be used in humans. Phenbenzamine (Antergan) was the first clinically useful antihistamine and was introduced for medical use in 1942. Subsequently, many other antihistamines were developed and marketed.

(Benadryl) was synthesized in 1943, tripelennamine (Pyribenzamine) was patented in 1946, and

(Phenergan) was synthesized in 1947 and launched in 1949. By 1950, at least 20 antihistamines had been marketed. Chlorphenamine (Piriton), a less sedating antihistamine, was synthesized in 1951, and hydroxyzine (Atarax, Vistaril), an antihistamine used specifically as a sedative and tranquilizer, was developed in 1956. The first non-sedating antihistamine was

terfenadine Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel (now Sanofi) and was marketed under various brand names, including Seldane in the United States, Triluda ...

(Seldane) and was developed in 1973. Subsequently, other non-sedating antihistamines like

loratadine Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in drug combinations such as loratadine/pseudoephedrine, in whic ...

(Claritin),

cetirizine Cetirizine is a second-generation antihistamine, second-generation Peripherally selective antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty ...

(Zyrtec), and

fexofenadine Fexofenadine, sold under the brand name Allegra among others, is an antihistamine medication used in the treatment of allergy symptoms such as allergic rhinitis and urticaria. Therapeutically, fexofenadine is a selective peripheral H1 blocke ...

(Allegra) were developed and introduced. The introduction of the first-generation antihistamines marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H₁ receptor antagonists and also to the development of H₂ receptor antagonists, where H₁-antihistamines affected the nose and the H₂-antihistamines affected the stomach. This history has led to contemporary research into drugs which are H₃ receptor antagonists and which affect the H₄ receptor antagonists. Most people who use an H₁ receptor antagonist to treat allergies use a second-generation drug.

Society and culture

The United States government removed two second generation antihistamines,

and astemizole, from the market based on evidence that they could cause heart problems.

Research

Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist is mostly short-term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long-term allergies who take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is no research comparing the relative efficacy of these drugs.

Special populations

In 2020, the UK

National Health Service The National Health Service (NHS) is the term for the publicly funded health care, publicly funded healthcare systems of the United Kingdom: the National Health Service (England), NHS Scotland, NHS Wales, and Health and Social Care (Northern ...

wrote that " st people can safely take antihistamines" but that " me antihistamines may not be suitable" for young children, the pregnant or breastfeeding, for those taking other medicines, or people with conditions "such as heart disease, liver disease, kidney disease or epilepsy". Most studies of antihistamines reported on people who are younger, so the effects on people over age 65 are not as well understood. Older people are more likely to experience drowsiness from antihistamine use than younger people. Continuous and/or cumulative use of

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

medications, including first-generation antihistamines, is associated with higher risk for cognitive decline and dementia in older people. Also, most of the research has been on caucasians and other ethnic groups are not as represented in the research. The evidence does not report how antihistamines affect women differently than men. Different studies have reported on antihistamine use in children, with various studies finding evidence that certain antihistamines could be used by children 2 years of age, and other drugs being safer for younger or older children.

Potential uses studied

Research regarding the effects of commonly used medications upon certain cancer therapies has suggested that when consumed in conjunction with immune checkpoint inhibitors some may influence the response of subjects to that particular treatment whose T-cell functions were failing in anti-tumor activity. Upon study of records in mouse studies associated with 40 common medications ranging from antibiotics, antihistamines, aspirin, and hydrocortisone, that for subjects with melanoma and lung cancers, fexofenadine, one of three medications, along with loratadine, and cetirizine, that target histamine receptor H1 (HRH1), demonstrated significantly higher survival rates and had experienced restored T-cell anti-tumor activity, ultimately inhibiting tumor growth in the subject animals.Manjarrez, Alejandra Manjarrez,
Over-the-Counter Antihistamines Could Help Against Cancer
', The Scientist, November 24, 2021 Such results encourage further study in order to see whether results in humans is similar in combating resistance to immunotherapy.

References

External links

*
Antihistamine
information at Allergy UK {{DEFAULTSORT:Histamine Antagonist Vasoconstrictors

Medical uses

Types

H1-antihistamines

List of H1 antagonists/inverse agonists

H2-antihistamines

H3-antihistamines

H4-antihistamines

Atypical antihistamines

Histidine decarboxylase inhibitors

Mast cell stabilizers

History

Society and culture

Research

Special populations

Potential uses studied

See also

References

External links

H₁-antihistamines

List of H₁ antagonists/inverse agonists

H₂-antihistamines

H₃-antihistamines

H₄-antihistamines