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 inhalat ...
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, i ...
,
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 exposu ...
,
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 symptoms ...
, 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 derma ...
.
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 breathing. ...
,
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 and ...
, 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-lasti ...
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 gametophyt ...
,
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 current ...
, 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, cou ...
,
sinusitis
Sinusitis, also known as rhinosinusitis, is inflammation of the nasal mucosa, mucous membranes that line the paranasal sinuses, sinuses resulting in symptoms that may include thick Mucus#Respiratory system, nasal mucus, a nasal congestion, plugg ...
, 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, cough ...
.
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 discovered in ...
receptor that they act upon. The two largest classes of antihistamines are
H1-antihistamines and
H2-antihistamines.
H
1-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 par ...
,
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 mus ...
, 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 vessel ...
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 the ...
. H
2-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 organ (biology), organs of the digestive syste ...
, 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 agon ...
at histamine receptors.
Only a few currently marketed H
1-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 (lymph ...
), 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 showin ...
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 derma ...
— 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 splitting ...
.
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 ...
(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 e ...
s,
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 ...
, glandular cells,
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 vessel ...
, 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,
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 and ...
, 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 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, black ...
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
H
1-antihistamines refer to compounds that inhibit the activity of the
H1 receptor.
Since the H
1 receptor exhibits
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 ...
, H
1-antihistamines can be either 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 ...
s or
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 ...
s.
Normally, histamine binds to the H
1 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 H
1 receptor, but it was previously thought that they were antagonists.
Clinically, H
1-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
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 ...
-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 H
1-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 prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
; 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 a vein ...
and
doxylamine
Doxylamine, sold under the brand name Unisom among others, is an antihistamine medication which is used in the treatment of insomnia and allergies. In combination with pyridoxine ( vitamin B6), it is also used to treat morning sickness in pre ...
, may therefore 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, ...
. H
1-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.,
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 discovered in ...
) binding at the H
1 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 us ...
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 i ...
and to some extent with non-opioid ones as well. The most common antihistamines utilized for this purpose include
hydroxyzine
Hydroxyzine, sold under the brand names Atarax, Vistaril and others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or in ...
,
promethazine
Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...
(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 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 drug ...
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 f ...
,
orphenadrine, 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 h ...
s cross the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
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 case ...
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, ...
s.
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 a ...
*
Alimemazine
Alimemazine (INN), also known as trimeprazine, (brand names Nedeltran, Panectyl, Repeltin, Therafene, Theraligene, Theralen, Theralene, Vallergan, Vanectyl, and Temaril), commonly provided as a tartrate salt, is a phenothiazine derivative that is ...
(a
phenothiazine
Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...
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 those ...
,
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 excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...
)
*
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
Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 ...
(
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 ...
)
*
Azelastine
*
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 histam ...
*
Bromodiphenhydramine
Bromazine, sold under the brand names Ambodryl, Ambrodil, and Deserol among others, also known as bromodiphenhydramine, is an antihistamine and anticholinergic medication of the ethanolamine class. It is an analogue of diphenhydramine with a br ...
*
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 as ...
*
Buclizine
Buclizine is an antihistamine and anticholinergic of the diphenylmethylpiperazine group. It is considered to be an antiemetic, similar to meclizine.
In the United Kingdom, buclizine is one of three drugs contained in Migraleve tablets, marketed ...
*
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
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 dis ...
(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 ma ...
, also used as an
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 ...
)
*
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 acu ...
(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 ma ...
, 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. R ...
(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. The vast majority of the region is covered by Russ ...
)
*
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.
Cinnariz ...
(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 d ...
and
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 ...
)
*
Clemastine
*
Clomipramine
Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used for the treatment of obsessive–compulsive disorder, panic disorder, major depressive disorder, and chronic pain. It may increase th ...
(
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 ...
)
*
Clozapine
Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...
(
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
Cyclizine, sold under a number of brand names, is a medication used to treat and prevent nausea, vomiting and dizziness due to motion sickness or vertigo. It may also be used for nausea after general anaesthesia or that which developed from opio ...
*
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 an ...
*
Desloratadine
*
Dexbrompheniramine
Dexbrompheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It is the pharmacologically active dextrorotatory isomer of brompheniramine. It was formerly marketed in comb ...
*
Dexchlorpheniramine
Dexchlorpheniramine (trade name Polaramine) is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It is the pharmacologically active dextrorotatory isomer of chlorpheniramine.
It c ...
*
Dimenhydrinate
Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter drug used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine, an ethanolamine derivative, and 8-chloroth ...
(used as an
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 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 d ...
)
*
Dimetindene
Dimetindene , also sold under the brand name Fenistil, is an antihistamine/anticholinergic. It is a first generation selective H1 antagonist. Dimetindene is an atypical first generation H1 antagonist as it only minimally passes across the bloodâ ...
*
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 a vein ...
(Benadryl)
*
Dosulepin
Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the ...
(
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 ...
)
*
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 pre ...
(
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 ...
)
*
Doxylamine
Doxylamine, sold under the brand name Unisom among others, is an antihistamine medication which is used in the treatment of insomnia and allergies. In combination with pyridoxine ( vitamin B6), it is also used to treat morning sickness in pre ...
(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
A prescription drug (also prescription medication or prescripti ...
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 t ...
)
*
Ebastine
Ebastine is a H1 antihistamine with low potential for causing drowsiness.
It does not penetrate the blood–brain barrier to a significant amount and thus combines an effective block of the histamine H1 receptor, H1 receptor in peripheral bio ...
*
Embramine
*
Fexofenadine
Fexofenadine, sold under the brand name Allegra among others, is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever and urticaria.
Therapeutically, fexofenadine is a selective peripheral H1 block ...
(Allegra/Telfast)
*
Hydroxyzine
Hydroxyzine, sold under the brand names Atarax, Vistaril and others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or in ...
(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 anxi ...
and 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 d ...
; 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. The drug is also used to treat bedwetting. ...
(
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 ...
)
*
Ketotifen
Ketotifen, sold under the brand name Zaditor among others, is a second-generation noncompetitive H1-antihistamine and mast cell stabilizer. It is most commonly sold as a salt with fumaric acid, ketotifen fumarate, and is available in two forms. I ...
*
Levocabastine
Levocabastine (trade name Livostin or Livocab, depending on the region) is a selective second-generation H1 receptor antagonist which was discovered at Janssen Pharmaceutica in 1979. It is used for allergic conjunctivitis.
As well as acting as ...
(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
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 chlorpro ...
(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 ma ...
)
*
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 combination with pseudoephedrine, a decongestant, known as lora ...
(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 an ...
)
*
Meclizine
Meclizine, sold under the brand name Bonine, among others, is an antihistamine used to treat motion sickness and dizziness (vertigo). It is taken by mouth. Effects generally begin in an hour and last for up to a day.
Common side effects incl ...
(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 closely ...
(
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 an ...
)
*
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 ...
(
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 an ...
, 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 ta ...
(
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: Zyprexa)
*
Olopatadine
Olopatadine, sold under the brand name Opatanol among others, is a 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 generally resul ...
(used locally)
*
Orphenadrine (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, Italy ...
(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 ma ...
)
*
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
Pheniramine (trade name Avil among others) is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It has relatively strong sedative effects, and may sometimes be used off-label as an ...
*
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 f ...
*
Promethazine
Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...
(Phenergan)
*
Pyrilamine
Mepyramine, also known as pyrilamine, is a Antihistamine#H1-receptor antagonists, first generation antihistamine, targeting the Histamine H1 receptor, H1 receptor as an inverse agonist. Mepyramine rapidly permeates the brain, often causing drowsi ...
(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 ...
(
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: Seroquel)
*
Rupatadine
Rupatadine is a second generation antihistamine and platelet-activating factor antagonist used to treat allergies. It was discovered and developed by and is marketed as Rupafin and under several other trade names.
Medical uses
Rupatadine fum ...
(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, fe ...
(SARI antidepressant/anxiolytic/hypnotic with mild H
1 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
Triprolidine is an over-the-counter antihistamine with anticholinergic properties. It is used to combat the symptoms associated with allergies and is sometimes combined with other cold medications designed to provide general relief for flu-like ...
H2-antihistamines
H
2-antihistamines, like H
1-antihistamines, exist as
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 ...
s and neutral
antagonists
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
. They act on
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 of the ...
s of the
gastric
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 ...
mucosa, which are part of the endogenous signaling pathway for
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 ...
secretion. Normally, histamine acts on H
2 to stimulate acid secretion; drugs that inhibit H
2 signaling thus reduce the secretion of gastric acid.
H
2-antihistamines are among first-line therapy to treat
gastrointestinal condition
Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the liver ...
s 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 i ...
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 rec ...
*
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-Elli ...
*
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
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 i ...
*
Ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. I ...
*
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
Gastritis is infl ...
*
Tiotidine
H3-antihistamines
An H
3-antihistamine is a classification of
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 inhalat ...
used to inhibit the action of
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 discovered in ...
at the
H3 receptor. H
3 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
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 discovered in ...
. 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 syn ...
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. Part ...
via stimulation of H
1 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 of ...
. Consequently, unlike the H
1-antihistamines which are sedating, H
3-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 H
3-antihistamines include:
*
Clobenpropit
Clobenpropit is a histamine H3 receptor antagonist. It has neuroprotective effects via stimulation of GABA release in brain cells ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, ...
*
ABT-239
*
Ciproxifan
*
Conessine
*
A-349,821
A-349,821 is a potent and selective Histamine H3 receptor, histamine H3 receptor Receptor antagonist, antagonist (or possibly an inverse agonist). It has nootropic effects in animal studies, although there do not appear to be any plans for clinic ...
.
*
Thioperamide
Thioperamide is a potency (pharmacology), potent Histamine H4 receptor, HRH4 antagonist and binding selectivity, selective histamine H3 receptor, HRH3 receptor antagonist, antagonist capable of crossing the blood–brain barrier.
It was used by Je ...
H4-antihistamines
H
4-antihistamines inhibit the activity of the
H4 receptor.
Examples:
*
Thioperamide
Thioperamide is a potency (pharmacology), potent Histamine H4 receptor, HRH4 antagonist and binding selectivity, selective histamine H3 receptor, HRH3 receptor antagonist, antagonist capable of crossing the blood–brain barrier.
It was used by Je ...
*
JNJ 7777120
JNJ-7777120 was a drug being developed by Johnson & Johnson Pharmaceutical Research & Development which acts as a potent and selective antagonist at the histamine H4 receptor. It has anti-inflammatory effects, and has been demonstrated to be su ...
*
VUF-6002
VUF-6002 (JNJ-10191584) is a drug which acts as a potent and selective antagonist at the histamine H4 receptor. It has anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Ant ...
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 neurotransmis ...
:
*
Tritoqualine
Tritoqualine, also known as hypostamine, is an inhibitor of the enzyme histidine decarboxylase and therefore an atypical antihistamine, used for the treatment of urticaria and allergic rhinitis
Rhinitis, also known as coryza, is irritation a ...
*
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 par ...
stabilizers are drugs which prevent mast cell
degranulation.
*
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
Nedocromil sodium is a medication considered as 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 dro ...
*
β-agonists
History
The first H
1 receptor antagonists were discovered in the 1930s and these drugs were marketed in the 1940s.
Piperoxan
Piperoxan, also known as benodaine, was the first antihistamine to be discovered. This compound, derived from benzodioxan, was prepared in the early 1930s by Daniel Bovet and Ernest Fourneau at the Pasteur Institute in France. Formerly investiga ...
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 subst ...
to be used in humans.
Phenbenzamine
Phenbenzamine, sold under the brand name Antergan and known by the former developmental code name RP-2339, is an antihistamine of the ethylenediamine class which also has anticholinergic properties. It was introduced in 1941 or 1942 and was the f ...
(Antergan) was the first clinically useful antihistamine and was introduced for medical use in 1942.
Subsequently, many other antihistamines were developed and marketed.
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 a vein ...
(Benadryl) was synthesized in 1943,
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 ...
(Pyribenzamine) was patented in 1946, and
promethazine
Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...
(Phenergan) was synthesized in 1947 and launched in 1949.
By 1950, at least 20 different antihistamines had been marketed.
Chlorphenamine (Piriton), a less sedating antihistamine, was synthesized in 1951, and
hydroxyzine
Hydroxyzine, sold under the brand names Atarax, Vistaril and others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or in ...
(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-Aventis) and was marketed under various brand names, including Seldane in the United States, Tr ...
(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 combination with pseudoephedrine, a decongestant, known as lora ...
(Claritin),
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), and
fexofenadine
Fexofenadine, sold under the brand name Allegra among others, is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever and urticaria.
Therapeutically, fexofenadine is a selective peripheral H1 block ...
(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 H
1-antihistamines affected the nose and the H
2-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 H
1 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
Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel (now Sanofi-Aventis) and was marketed under various brand names, including Seldane in the United States, Tr ...
and
astemizole
Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It was withdrawn from the m ...
, 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.
See also
*
Antileukotriene
An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor (arachidonate 5-lipoxygenase) or leukotriene receptor antagonist (cysteinyl leukot ...
*
Immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
References
External links
*
Antihistamineinformation at Allergy UK
{{DEFAULTSORT:Histamine Antagonist
Vasoconstrictors