Antihistamines are
drugs which treat
allergic rhinitis,
common cold,
influenza, 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 (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, or
hives caused by
pollen,
dust mites, 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
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 receptors in the body.
In this sense of the word, antihistamines are subclassified according to the
histamine 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,
smooth muscle, 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 vesse ...
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. H
2-antihistamines bind to
histamine H2 receptors in the upper
gastrointestinal tract, 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 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). Other antihistamines also target
H3 receptors and
H4 receptors.
Histamine receptors 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 or an
inverse agonist 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), 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
symptoms of an
allergic reaction — a runny nose and watery eyes. Histamine also promotes
angiogenesis.
Antihistamines suppress the histamine-induced
wheal response (swelling) and
flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on
nerves,
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 ve ...
, 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 vesse ...
, 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, 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, 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 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 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 antagonists or
inverse agonists.
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 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 is a common side effect of H
1-antihistamines that readily cross the
blood–brain barrier; 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
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) 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 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
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 ...
,
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 and similar
prodrug opioids),
phenyltoloxamine,
orphenadrine, and
tripelennamine; some may also have intrinsic analgesic properties of their own, orphenadrine being an example.
Second-generation antihistamines cross the
blood–brain barrier 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 drugs such as
bupropion and
benzodiazepines.
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 (a
phenothiazine used as
antipruritic,
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)
*
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)
*
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)
*
Azelastine
*
Bilastine
*
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 ...
*
Buclizine
*
Carbinoxamine
*
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 las ...
*
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 di ...
(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 m ...
)
*
Chlorprothixene (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 (first generation antihistamine marketed in
Eastern Europe)
*
Cinnarizine (also used for
motion sickness
Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include de ...
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 (
tricyclic antidepressant)
*
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 m ...
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 de ...
)
*
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 (
tricyclic antidepressant)
*
Doxepin (
tricyclic antidepressant)
*
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 ...
sedative)
*
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 ...
(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
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 ...
; trade names: Atarax, Vistaril)
*
Imipramine (
tricyclic antidepressant)
*
Ketotifen
*
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 (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 chlorpr ...
(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 ant ...
)
*
Meclizine (most commonly used as an antiemetic)
*
Mianserin (
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 ...
)
*
Mirtazapine (
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 ...
, 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 ...
(
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 (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
*
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
*
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 (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, f ...
(SARI antidepressant/anxiolytic/hypnotic with mild H
1 blockade action)
*
Tripelennamine
*
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 agonists and neutral
antagonists. 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 ...
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 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 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
*
Famotidine
*
Lafutidine
*
Nizatidine
Nizatidine is a histamine H2 receptor antagonist that inhibits stomach acid production, and is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease.
It was patented in 1980 and approved for medical use 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 ...
*
Roxatidine
*
Tiotidine
H3-antihistamines
An H
3-antihistamine is a classification of
drugs used to inhibit the action of
histamine 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 release in the brain triggers secondary release of excitatory neurotransmitters such as
glutamate and
acetylcholine 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% consistin ...
. Consequently, unlike the H
1-antihistamines which are sedating, H
3-antihistamines have
stimulant and cognition-modulating effects.
Examples of selective H
3-antihistamines include:
*
Clobenpropit
*
ABT-239
*
Ciproxifan
*
Conessine
*
A-349,821.
*
Thioperamide
H4-antihistamines
H
4-antihistamines inhibit the activity of the
H4 receptor.
Examples:
*
Thioperamide
*
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
Atypical antihistamines
Histidine decarboxylase inhibitors
Inhibit the action of
histidine decarboxylase:
*
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.
*
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 dr ...
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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 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.
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) was synthesized in 1943,
tripelennamine (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 ...
(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 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
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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 leuko ...
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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
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Antihistamineinformation at Allergy UK
{{DEFAULTSORT:Histamine Antagonist
Vasoconstrictors