Antihistamines are

drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalati ...

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. Signs and symptoms include a runny or stuffy nose, sneezing, red, ...

common cold The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after expos ...

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 symptom ...

, and other

allergies Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermat ...

. Typically, people take antihistamines as an inexpensive,

generic Generic or generics may refer to: In business * Generic term, a common name used for a range or class of similar things not protected by trademark * Generic brand, a brand for a product that does not have an associated brand or trademark, other ...

(not patented) drug that can be bought without a prescription and provides relief from

nasal congestion Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathin ...

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 an ...

, or

hives Hives, also known as urticaria, is a kind of skin rash with red, 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 does not leave any long-last ...

caused by

pollen Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametop ...

dust mites House dust mites (HDM, or simply dust mites) are various species of acariform mites belonging to the family Pyroglyphidae that are found in association with dust in dwellings. They are known for causing allergies. Biology Species The curren ...

, or animal allergy 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 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 wheezing, co ...

sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...

, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use. Although people typically use the word "antihistamine" to describe drugs for treating allergies, doctors 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. There are four known histamine receptors: * H1 receptor * H2 receptor * H3 receptor * H4 receptor Comparison There ...

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, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...

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 p ...

smooth muscle Smooth muscle is an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit ...

, and

endothelium The endothelium 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 rest of the ve ...

in the body as well as in the

tuberomammillary nucleus The tuberomammillary nucleus (TMN) is a histaminergic nucleus located within the posterior third of the hypothalamus. It consists of, largely, histaminergic neurons (i.e., histamine-releasing neurons) and is involved with the control of arousal, l ...

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 in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, motion sickness, or

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

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 th ...

. 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 digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

, primarily in the

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

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

gastric acid Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...

conditions (e.g.,

peptic ulcers Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...

and

acid reflux Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...

). 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. There are four known histamine receptors: * H1 receptor * H2 receptor * H3 receptor * H4 receptor Comparison There ...

s exhibit

constitutive activity In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recepto ...

, 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 rece ...

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 ago ...

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

Medical uses

Histamine makes blood vessels more permeable (

vascular permeability Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells ( lymp ...

), causing fluid to escape from

capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

into tissues, which leads to the classic

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...

s of an

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

— 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 by processes of sprouting and splittin ...

. 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, nails, and related muscle and glands. The major function of this sy ...

(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) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the ...

s, vascular smooth muscle, 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 par ...

s. Antihistamines can also help correct

Eustachian Tube dysfunction Eustachian tube dysfunction (ETD) is a disorder where pressure abnormalities in the middle ear result in symptoms. Signs and symptoms Symptoms include aural fullness, ears popping, a feeling of pressure in the affected ear(s), a feeling that the ...

, thereby helping correct problems such as muffled hearing, fullness in the ear and even

tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

Itch Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

ing,

, and inflammatory responses are suppressed by antihistamines that act on

H1-receptor The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the ...

s. In 2014, antihistamines such as

desloratadine Desloratadine (trade names Clarinex and Aerius) is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine. It was patented in 1984 and came into medical use in 2001. Medical uses Deslora ...

were found to be effective to complement standardized treatment of

acne Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...

due to their

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...

properties and their ability to suppress

sebum A sebaceous 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 in the greatest nu ...

production.

Types

H₁-antihistamines

H₁-antihistamines refer to compounds that inhibit the activity of the H₁ receptor. Since the H₁ receptor exhibits

, 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, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic der ...

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 border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

; some of these drugs, such as

diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...

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 protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

, 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 substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

analgesics An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

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

and similar

prodrug A prodrug is a 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 used to improve how the dru ...

opioids),

phenyltoloxamine Phenyltoloxamine is an antihistamine with sedative and analgesic effects. It is available in combination with other drugs such as paracetamol (acetominophen). Common use Phenyltoloxamine is widely used in preparations as an enhancing agent fo ...

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 i ...

, and

tripelennamine Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitis, and urticaria, but is now less ...

; 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 ...

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. Additionally, some second-generation antihistamines, notably

cetirizine Cetirizine, sold under the brand name Zyrtec among others, is a second-generation antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty minutes a ...

, can interact with CNS

psychoactive A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

drugs such as

bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...

and

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

H₁ antagonists/inverse agonists

* Acrivastine * Alimemazine (a phenothiazine used as

antipruritic Antipruritics, abirritants, or anti-itch drugs, are medications that inhibit the itching (Latin: '' pruritus'') often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like ...

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 m ...

and

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but ...

) *

Amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...

(

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

) * Amoxapine (

) *

Azelastine Azelastine, sold under the brand name Optivar among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis. Other uses may include asthm ...

Bilastine Bilastine is an antihistamine medication used to treat hives (urticaria) and inflammation of the eye (allergic conjunctivitis) caused by an allergy. It is a second-generation antihistamine and takes effect by selectively inhibiting the histami ...

* Bromodiphenhydramine *

Brompheniramine Brompheniramine, sold under the brand name Dimetapp among others, is a first-generation antihistamine drug of the propylamine (alkylamine) class. It is indicated for the treatment of the symptoms of the common cold and allergic rhinitis, such a ...

* Buclizine *

Carbinoxamine Carbinoxamine is an antihistamine and anticholinergic agent. It is used for hay fever, vasomotor rhinitis, mild urticaria, angioedema, dermatographism and allergic conjunctivitis. Carbinoxamine is a histamine antagonist, specifically an H1-anta ...

Cetirizine Cetirizine, sold under the brand name Zyrtec among others, is a second-generation antihistamine used to treat allergic rhinitis (hay fever), dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty minutes a ...

(Zyrtec) * 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 by mouth. The medication takes effect within two hours and lasts ...

* Chlorpromazine (low-potency typical antipsychotic, also used as an

) * Chlorprothixene (low-potency typical antipsychotic, trade name: Truxal) *

Chloropyramine Chloropyramine is a classical first-generation antihistamine drug approved in Eastern European countries (like Russia) for the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions. Re ...

(first generation antihistamine marketed in

Eastern Europe Eastern Europe is a subregion of the European continent. As a largely ambiguous term, it has a wide range of geopolitical, geographical, ethnic, cultural, and socio-economic connotations. The vast majority of the region is covered by Russia, whi ...

) *

Cinnarizine Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. It is prescribed for nausea and vomiting due to motion sickness or other sources such as chemotherapy, vertigo, or Ménière's disease. Cinnarizi ...

(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 de ...

and

) *

Clemastine Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects. Like all first-generation antihistamines, it is sedating. Patented in 196 ...

* Clomipramine (

) * Clozapine (

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 major tranquilizers and ne ...

; trade name: Clozaril) * Cyclizine * Cyproheptadine *

Desloratadine Desloratadine (trade names Clarinex and Aerius) is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine. It was patented in 1984 and came into medical use in 2001. Medical uses Deslora ...

* Dexbrompheniramine * Dexchlorpheniramine * Dimenhydrinate (used as an

and for

) * Dimetindene *

Diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...

(Benadryl) * Dosulepin (

) *

Doxepin Doxepin is a medication falling in the tricyclic antidepressant (TCA) class used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For label updates seFDA index page for NDA 022036/ref> For hives it is a less ...

(

) * Doxylamine (most commonly used as an

over-the-counter drug 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 prescr ...

) * Ebastine * Embramine * Fexofenadine (Allegra/Telfast) * Hydroxyzine (also used as an

anxiolytic An anxiolytic (; also antipanic or antianxiety 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 anxiet ...

and for

; trade names: Atarax, Vistaril) * Imipramine (

) * Ketotifen * Levocabastine (Livostin/Livocab) *

Levocetirizine Levocetirizine, sold under the brand name Xyzal among others, is a second-generation antihistamine used for the treatment of allergic rhinitis (hay fever) and long term hives of unclear cause. It is less sedating than older antihistamines. It is ...

(Xyzal) * Levomepromazine (low-potency typical antipsychotic) * Loratadine (Claritin) *

Maprotiline Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary am ...

(

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 rings of atoms, and are closely related to the tricyclic ant ...

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

Mianserin Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant that is used primarily in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant (TeCA). Mianserin is closel ...

(

) *

Mirtazapine Mirtazapine, sold under the brand name Remeron amongst others, is an atypical antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is o ...

(

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

Olanzapine Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is t ...

(

; trade name: Zyprexa) * Olopatadine (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 i ...

(a close relative of diphenhydramine used mainly as a skeletal muscle relaxant and anti-Parkinsons agent) * Periciazine (low-potency typical antipsychotic) *

Phenindamine Phenindamine (Nolahist, Thephorin) is an antihistamine and anticholinergic closely related to cyproheptadine. It was developed by Hoffman-La Roche in the late 1940s. It is used to treat symptoms of the common cold and allergies, such as sneezing ...

* Pheniramine *

Phenyltoloxamine Phenyltoloxamine is an antihistamine with sedative and analgesic effects. It is available in combination with other drugs such as paracetamol (acetominophen). Common use Phenyltoloxamine is widely used in preparations as an enhancing agent fo ...

* Promethazine (Phenergan) *

Pyrilamine Mepyramine, also known as pyrilamine, is a first generation antihistamine, targeting the H1 receptor as an inverse agonist. Mepyramine rapidly permeates the brain, often causing drowsiness. It is often sold as a maleate salt, pyrilamine maleate. ...

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

Quetiapine Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...

(

; trade name: Seroquel) * Rupatadine (Alergoliber) *

Trazodone Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally. Common side-effects include dry mouth, f ...

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

Tripelennamine Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitis, and urticaria, but is now less ...

* Triprolidine

H₂-antihistamines

H₂-antihistamines, like H₁-antihistamines, exist as

s 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

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 (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines ...

s and

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

. 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. The development of longer-acting H2 r ...

* Famotidine *

Lafutidine Lafutidine (INN) is a second generation histamine H2 receptor antagonist having multimodal mechanism of action and used to treat gastrointestinal disorders. It is marketed in South Korea, Japan and India. Medical use Lafutidine is used to trea ...

* Nizatidine * Ranitidine * Roxatidine * 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 located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the au ...

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; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

and

acetylcholine Acetylcholine (ACh) is an organic chemical 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. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

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

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

and cognition-modulating effects. Examples of selective H₃-antihistamines include: * Clobenpropit * ABT-239 * Ciproxifan * Conessine * A-349,821. *

Thioperamide Thioperamide is a potent HRH4 antagonist and selective HRH3 antagonist capable of crossing the blood–brain barrier. It was used by Jean-Charles Schwartz in his early experiments regarding the H3 receptor. Thioperamide was found to be an ant ...

H₄-antihistamines

H₄-antihistamines inhibit the activity of the H₄ receptor. Examples: *

* 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 21.2, and catalyzes the decarboxylation of histidine to form histamine. In mammals, histamine is an important biogenic amine with regulatory roles in neurotransmi ...

: * 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 tanni ...

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 par ...

stabilizers are drugs which prevent mast cell

degranulation Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including gra ...

. *

cromolyn sodium Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. ...

* Nedocromil * β-agonists

History

The first H₁ receptor antagonists were discovered in the 1930s and these drugs were marketed in the 1940s. Piperoxan was discovered in 1933 and was the first compound with antihistamine effects to be identified. However, 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 sub ...

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,

(Pyribenzamine) was patented in 1946, and promethazine (Phenergan) was synthesized in 1947 and launched in 1949. By 1950, at least 20 different antihistamines had been marketed.

Chlorphenamine 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 by mouth. The medication takes effect within two hours and lasts ...

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

(Zyrtec), and fexofenadine (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. Currently most people who use an H₁ receptor antagonist to treat allergies use a second- or third-generation drug.

Society and culture

The United States government removed two second generation antihistamines, terfenadine 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 umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...

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. 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 Antihistamines, Vasoconstrictors

Medical uses

Types

H1-antihistamines

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

H₁ antagonists/inverse agonists

H₂-antihistamines

H₃-antihistamines

H₄-antihistamines