5-HT2A receptor
Encyclopedia
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). This is the main excitatory receptor subtype among the GPCRs for serotonin
(5-HT), although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex
and the orbitofrontal cortex
. This receptor was given importance first as the target of psychedelic
drugs like LSD
. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic
drugs, especially the atypical
ones.
5-HT2A also happens to be a necessary receptor for the spread of the human polyoma virus called JC virus
.
Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked chronic administration of SSRIs and classical antipsychotics. Deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These finds suggest that post-synaptic 5-HT2A overdensity is involved in the pathogenesis of depression.
could be blocked by morphine
, whilst the remainder of the response was inhibited by dibenzyline
leading to the naming of M and D receptors respectively. 5-HT2A is thought to correspond to what was originally described as D subtype of 5-HT receptors by Gaddum and Picarelli. In the pre-molecular-cloning era when radioligand
binding and displacement was the only major tool, spiperone and LSD were shown to label two different serotonin receptors, and neither of them displaced morphine, leading to naming of the 5-HT1
, 5-HT2
and 5-HT3
receptors, corresponding to high affinity sites from LSD
, spiperone
and morphine respectively. Later it was shown that the 5-HT2 was very close to 5-HT1C and thus were clubbed together, renaming the 5-HT2 into 5-HT2A. Thus the 5-HT2 receptor family is composed of three separate molecular entities: the 5-HT2A (erstwhile 5-HT2 or D), the 5-HT2B (erstwhile 5-HT2F) and the 5-HT2C (erstwhile 5-HT1C) receptors.
(CNS).
It is expressed near most of the serotoninergic terminal rich areas, including neocortex
(mainly prefrontal, parietal, and somatosensory cortex) and the olfactory tubercle
. Especially high concentrations of this receptor on the apical dendrite
s of pyramidal cell
s in layer V of the cortex may modulate cognitive processes, by enhancing glutamate release followed by a complex range of interactions with the 5-HT1A
, GABAA, adenosine A1, AMPA
, mGluR2/3, mGlu5
, and OX2
receptors. In the rat cerebellum, the protein has also been found in the Golgi cell
s of the granular layer
, and in the Purkinje cell
s.
In the periphery, it is highly expressed in platelets and many cell types of the cardiovascular system, in fibroblast
s, and in neurons of the peripheral nervous system. Additionally, 5-HT2A mRNA expression has been observed in human monocytes.
(PLC) activity, which subsequently promotes the release of diacylglycerol
(DAG) and inositol triphosphate
(IP3), which in turn stimulate protein kinase C
(PKC) activity and Ca2+ release.
There are many additional signal cascade components that include the formation of arachidonic acid
through PLA2 activity, activation of phospholipase D
, Rho
/Rho kinase, and ERK
pathway activation initiated by agonist stimulation of the receptor.
is necessary for the effects of the "classic" psychedelic
s like LSD
, psilocin
and mescaline
, which act as full or partial agonists at this receptor, and represent the three main classes of 5-HT2A agonists, the ergoline
s, tryptamine
s and phenethylamine
s, respectively. A very large family of derivatives from these three classes has been developed, and their structure-activity relationship
s have been extensively researched. Agonists acting at 5-HT2A receptors located on the apical dendrite
s of pyramidal cell
s within regions of the prefrontal cortex
are believed to mediate hallucinogenic activity.
, a congener of methylergonovine
, used in treatment of migraine
blocks 5-HT2A and 5-HT2C receptors, but sometimes acts as partial agonist, in some preparations. The atypical antipsychotic aripiprazole
is also a weak partial agonist.
. This has led to the development of compounds such as AL-34662
that are hoped to reduce pressure inside the eyes but without crossing the blood-brain barrier
and producing hallucinogenic side effects. Animal studies with this compound showed it to be free of hallucinogenic effects at doses up to 30 mg/kg, although several of its more lipophilic analogues did produce the head twitch response known to be characteristic of hallucinogenic effects in rodents.
may differentially activate the transductional pathways
(see above). Studies evaluated the activation of two effectors
, PLC
and PLA2
, by means of their second messengers. Compounds displaying more pronounced functional selectivity
are 2,5-DMA and 2C-N
. The former induces IP
accumulation without activating the PLA2 mediated response, while the latter elicits AA
release without activating the PLC mediated response.
Recent research has suggested potential signaling differences within the somatosensory cortex between 5-HT2A agonists that produce headshakes in the mouse
and those that do not, such as lisuride
, as these agents are also non-hallucinogenic in humans despite being active 5-HT2A agonists.
The difference in signal transduction between the two 5-HT2A agonists serotonin and DOI
may be due to the presence of the intracellular proteins called β-arrestin
s, more specifically arrestin beta 2
.
The 5-HT2A receptors is coded by the HTR2A gene.
In humans the gene is located on chromosome 13.
The gene has previously been called just HTR2 until the description of two related genes HTR2B and HTR2C.
Several interesting polymorphism
s have been identified for HTR2A:
A-1438G (rs6311
),
C102T (rs6313
) and
His452Tyr (rs6314
).
Many more polymorphisms exist for the gene.
A 2006 paper listed 255.
and major depressive disorder.
A weak link with an odds ratio
of 1.3 has been found between the T102C polymorphism and schizophrenia
.
This polymorphism has also been studied in relation to suicide
attempts, with a study finding excess of the C/C genotypes among the suicide attempters. A number of other studies were devoted to finding an association of the gene with schizophrenia, with diverging results.
These individual studies may, however, not give a full picture: A review from 2007 looking at the effect of different SNPs reported in separate studies stated that "genetic association studies [of HTR2A gene variants with psychiatric disorders] report conflicting and generally negative results" with no involvement, small or a not replicated role for the genetic variant of the gene.
may benefit more than others if they have one particular genotype.
In this study 768 single nucleotide polymorphism
(SNP) across 68 genes were investigated and a SNP—termed rs7997012
—in the second intron
of the HTR2A gene showed significant association with treatment outcome.
Genetics seems also to be associated to some extent with the amount of adverse events in treatment of major depression disorder.
and MDL 100,907
radioligand
s that binds to the neuroreceptor, e.g.,
one study reported a reduced binding of altanserin particularly in the hippocampus
in patients with major depressive disorder.
Another PET study reported increased altanserin binding in the caudate nuclei
in obsessive compulsive disorder patients compared to a healthy control group.
Patients with Tourette's syndrome have also been scanned and the study found an increased binding of altanserin for patients compared to healthy controls. The altanserin uptake decreases with age reflecting a loss of specific 5-HT2A receptors with age.
A study has also found a positive correlation among healthy subjects between altanserin binding and the personality trait neuroticism
as measured by the NEO PI-R personality questionnaire.
mediated endocytosis
of the human polyoma virus called JC virus
, the causative agent of progressive multifocal leukoencephalopathy
(PML), that enters cells like oligodendrocyte
s, astrocyte
s, B lymphocytes, and kidney epithelial cells. These cells need to express both the alpha 2-6–linked sialic acid
component of the 5HT2A receptor in order to endocytose JCV.
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(5-HT), although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex
Visual cortex
The visual cortex of the brain is the part of the cerebral cortex responsible for processing visual information. It is located in the occipital lobe, in the back of the brain....
and the orbitofrontal cortex
Orbitofrontal cortex
The orbitofrontal cortex is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making...
. This receptor was given importance first as the target of psychedelic
Psychedelic
The term psychedelic is derived from the Greek words ψυχή and δηλοῦν , translating to "soul-manifesting". A psychedelic experience is characterized by the striking perception of aspects of one's mind previously unknown, or by the creative exuberance of the mind liberated from its ostensibly...
drugs like LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
drugs, especially the atypical
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
ones.
5-HT2A also happens to be a necessary receptor for the spread of the human polyoma virus called JC virus
JC virus
The JC virus or John Cunningham virus is a type of human polyomavirus and is genetically similar to BK virus and SV40. It was discovered in 1971 and named using the two initials of a patient with progressive multifocal leukoencephalopathy...
.
Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked chronic administration of SSRIs and classical antipsychotics. Deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These finds suggest that post-synaptic 5-HT2A overdensity is involved in the pathogenesis of depression.
History
Serotonin receptors were split into two classes by Gaddum and Picarelli when it was discovered that some of the serotonin-induced changes in the gutGut (zoology)
In zoology, the gut, also known as the alimentary canal or alimentary tract, is a tube by which bilaterian animals transfer food to the digestion organs. In large bilaterians the gut generally also has an exit, the anus, by which the animal disposes of solid wastes...
could be blocked by morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, whilst the remainder of the response was inhibited by dibenzyline
Phenoxybenzamine
Phenoxybenzamine is a non-selective, irreversible alpha antagonist.-Uses:It is used in the treatment of hypertension, and specifically that caused by pheochromocytoma...
leading to the naming of M and D receptors respectively. 5-HT2A is thought to correspond to what was originally described as D subtype of 5-HT receptors by Gaddum and Picarelli. In the pre-molecular-cloning era when radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....
binding and displacement was the only major tool, spiperone and LSD were shown to label two different serotonin receptors, and neither of them displaced morphine, leading to naming of the 5-HT1
5-HT1 receptor
The 5-HT1 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT1 subfamily consists of five G protein-coupled receptors that are coupled to Gi/Go and mediate inhibitory neurotransmission, including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F...
, 5-HT2
5-HT2 receptor
The 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT2 subfamily consists of three G protein-coupled receptors which are coupled to Gq/G11 and mediate excitatory neurotransmission, including 5-HT2A, 5-HT2B, and 5-HT2C...
and 5-HT3
5-HT3 receptor
The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors , and the inhibitory neurotransmitter receptors for GABA and glycine...
receptors, corresponding to high affinity sites from LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
, spiperone
Spiperone
Spiperone is a psychoactive drug and research chemical belonging to the butyrophenone chemical class. It functions as a 5-HT1A, 5-HT2A, 5-HT7, and D2 receptor antagonist, and has been used to identify these receptors when labeled with tritium. It has negligible affinity for the 5-HT2C receptor...
and morphine respectively. Later it was shown that the 5-HT2 was very close to 5-HT1C and thus were clubbed together, renaming the 5-HT2 into 5-HT2A. Thus the 5-HT2 receptor family is composed of three separate molecular entities: the 5-HT2A (erstwhile 5-HT2 or D), the 5-HT2B (erstwhile 5-HT2F) and the 5-HT2C (erstwhile 5-HT1C) receptors.
Distribution
5-HT2A is expressed widely throughout the central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS).
It is expressed near most of the serotoninergic terminal rich areas, including neocortex
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
(mainly prefrontal, parietal, and somatosensory cortex) and the olfactory tubercle
Olfactory tubercle
The olfactory tubercle is a structure involved in Olfaction.It is present in humans, but much smaller than it is in some other animals.It is a frequent subject of research.-External links:...
. Especially high concentrations of this receptor on the apical dendrite
Apical dendrite
An apical dendrite is a dendrite that emerges from the apex of a pyramidal cell. Apical dendrites are one of two primary categories of dendrites, and they distinguish the pyramidal cells from spiny stellate cells in the cortices. Pyramidal cells are found in the prefrontal cortex, the hippocampus,...
s of pyramidal cell
Pyramidal cell
Pyramidal neurons are a type of neuron found in areas of the brain including cerebral cortex, the hippocampus, and in the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cortex and the corticospinal tract. Pyramidal neurons were first discovered and...
s in layer V of the cortex may modulate cognitive processes, by enhancing glutamate release followed by a complex range of interactions with the 5-HT1A
5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...
, GABAA, adenosine A1, AMPA
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
, mGluR2/3, mGlu5
Metabotropic glutamate receptor 5
Metabotropic glutamate receptor 5 is a protein that in humans is encoded by the GRM5 gene.- Function :The amino acid L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors...
, and OX2
Hypocretin (orexin) receptor 2
Orexin receptor type 2 , also known as hypocretin receptor type 2, is a protein that in humans is encoded by the HCRTR2 gene.- Function :...
receptors. In the rat cerebellum, the protein has also been found in the Golgi cell
Golgi cell
In neuroscience, Golgi cells are inhibitory interneurons found within the granular layer of the cerebellum. They were first identified as inhibitory by Eccles et al in 1964....
s of the granular layer
Granular layer
The term granular layer may refer to:*the granular layer of Tomes, seen in dentin of the teeth. When dry section of the root dentin of teeth are visualized under transmitted light, a granular layer is seen adjacent to cementum.It is believed to be caused by coalescing & looping of terminal portion...
, and in the Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
s.
In the periphery, it is highly expressed in platelets and many cell types of the cardiovascular system, in fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s, and in neurons of the peripheral nervous system. Additionally, 5-HT2A mRNA expression has been observed in human monocytes.
Signaling cascade
The 5-HT2A receptor is known primarily to couple to the Gαq signal transduction pathway. Upon receptor stimulation with agonist, Gαq and β-γ subunits dissociate to initiate downstream effector pathways. Gαq stimulates phospholipase CPhospholipase C
Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...
(PLC) activity, which subsequently promotes the release of diacylglycerol
Diglyceride
A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....
(DAG) and inositol triphosphate
Inositol triphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate , together with diacylglycerol , is a secondary messenger molecule used in signal transduction and lipid signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell...
(IP3), which in turn stimulate protein kinase C
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
(PKC) activity and Ca2+ release.
There are many additional signal cascade components that include the formation of arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
through PLA2 activity, activation of phospholipase D
Phospholipase D
Phospholipase D is an enzyme which is located in the plasma membrane and catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid , releasing the soluble choline headgroup into the cytosol...
, Rho
Rho family of GTPases
The Rho family of GTPases is a family of small signaling G protein , and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants...
/Rho kinase, and ERK
Extracellular signal-regulated kinases
In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...
pathway activation initiated by agonist stimulation of the receptor.
Effects
Physiological processes mediated by the receptor include:- CNS: neuronal excitation, behavioural effects, learning, anxiety
- smooth muscle: contraction (in gastrointestinal tractGastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
& bronchi) - vasoconstrictionVasoconstrictionVasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
/ vasodilatation - platelets: aggregation
- Activation of the 5-HT2A receptor with DOI produces superpotent anti-inflammatoryAnti-inflammatoryAnti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
effects in cardiovascular related tissues, as well as potent anti-inflammatory effects in non-cardiovascular tissues. Other 5-HT2A agonists like LSD also have potent anti-inflammatory effects against TNF-alpha-induced inflammationInflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. - Activation of the 5-HT2A receptor in hypothalamus causes increases in hormonal levels of oxytocinOxytocinOxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
, prolactinProlactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
, ACTH, corticosteroneCorticosteroneCorticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
, and reninReninRenin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
.
Agonists
Activation of the 5-HT2A receptorReceptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
is necessary for the effects of the "classic" psychedelic
Psychedelic
The term psychedelic is derived from the Greek words ψυχή and δηλοῦν , translating to "soul-manifesting". A psychedelic experience is characterized by the striking perception of aspects of one's mind previously unknown, or by the creative exuberance of the mind liberated from its ostensibly...
s like LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
, psilocin
Psilocin
Psilocin , an aromatic compound, sometimes also spelled psilocine, psilocyn, or psilotsin, is a psychedelic mushroom alkaloid. It is found in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin...
and mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....
, which act as full or partial agonists at this receptor, and represent the three main classes of 5-HT2A agonists, the ergoline
Ergoline
Ergoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs . Ergoline derivatives are used clinically for the purpose of vasoconstriction and in the treatment of migraines and Parkinson's disease...
s, tryptamine
Tryptamine
Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...
s and phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
s, respectively. A very large family of derivatives from these three classes has been developed, and their structure-activity relationship
Structure-activity relationship
The structure–activity relationship is the relationship between the chemical or 3D structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism...
s have been extensively researched. Agonists acting at 5-HT2A receptors located on the apical dendrite
Apical dendrite
An apical dendrite is a dendrite that emerges from the apex of a pyramidal cell. Apical dendrites are one of two primary categories of dendrites, and they distinguish the pyramidal cells from spiny stellate cells in the cortices. Pyramidal cells are found in the prefrontal cortex, the hippocampus,...
s of pyramidal cell
Pyramidal cell
Pyramidal neurons are a type of neuron found in areas of the brain including cerebral cortex, the hippocampus, and in the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cortex and the corticospinal tract. Pyramidal neurons were first discovered and...
s within regions of the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
are believed to mediate hallucinogenic activity.
Full agonists
- (R)-DOI2,5-Dimethoxy-4-iodoamphetamine2,5-dimethoxy-4-iodoamphetamine is a psychedelic drug and a substituted amphetamine of the phenethylamine family. It is also a powerful anti-inflammatory that is effective at doses on the order of 100 micrograms in humans, far below its effective dose as a psychedelic. Despite being a substituted...
- N-(2-hydroxybenzyl)-2C-I25I-NBOH25I-NBOH is a derivative of the phenethylamine derived hallucinogen 2C-I, discovered in 2006 by a team at Purdue University. It acts as a potent agonist for the 5HT2A receptor, with a Ki of 0.12nM at the human 5HT2A receptor, making it some 5x the potency of 2C-I itself...
and its 2-methoxy-analog25I-NBOMe25I-NBOMe is a derivative of the phenethylamine hallucinogen 2C-I, discovered in 2003 by Ralf Heim at the Free University of Berlin, and subsequently investigated in more detail by a team at Purdue University led by David Nichols.25I-NBOMe acts as a highly potent agonist for the human 5-HT2A... - TCB-2TCB-2TCB-2 is a hallucinogen, discovered in 2006 by a team at Purdue University where it has been named 2C-BCB. It is a conformationally-restricted derivative of the phenethylamine 2C-B, also a hallucinogen, and acts as a potent agonist for the 5-HT2A and 5-HT2C receptors with a Ki of 0.26nM at the...
- Br-DFLY.
Partial agonists
MethysergideMethysergide
Methysergide is a prescription drug used for prophylaxis of migraine headaches and is sold under the brand names Sansert and Deseril in 2 mg dosages.-Pharmacology:Methysergide interacts with serotonin receptors...
, a congener of methylergonovine
Methylergonovine
Methylergometrine is a synthetic analogue of ergonovine, a psychedelic alkaloid found in ergot, and many species of morning glory. It is a member of the ergoline family and chemically similar to LSD, ergine, ergometrine, and lysergic acid...
, used in treatment of migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
blocks 5-HT2A and 5-HT2C receptors, but sometimes acts as partial agonist, in some preparations. The atypical antipsychotic aripiprazole
Aripiprazole
Aripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression...
is also a weak partial agonist.
Peripherally selective agonists
One effect of 5-HT2A receptor activation is a reduction in intraocular pressure, and so 5-HT2A agonists can be useful for the treatment of glaucomaGlaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
. This has led to the development of compounds such as AL-34662
AL-34662
AL-34662 is an indazole derivative drug that is being developed for the treatment of glaucoma. It acts as a selective 5-HT2A receptor agonist, the same target as that of hallucinogenic drugs like psilocin, but unlike these drugs, AL-34662 was designed specifically as a peripherally selective drug,...
that are hoped to reduce pressure inside the eyes but without crossing the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and producing hallucinogenic side effects. Animal studies with this compound showed it to be free of hallucinogenic effects at doses up to 30 mg/kg, although several of its more lipophilic analogues did produce the head twitch response known to be characteristic of hallucinogenic effects in rodents.
Silent antagonists
- Although ergotErgotErgot or ergot fungi refers to a group of fungi of the genus Claviceps. The most prominent member of this group is Claviceps purpurea. This fungus grows on rye and related plants, and produces alkaloids that can cause ergotism in humans and other mammals who consume grains contaminated with its...
alkaloids are mostly nonspecific 5-HT receptor antagonists, a few ergot derivatives such as metergolineMetergolineMetergoline is a psychoactive drug of the ergoline chemical class which acts as a ligand for various serotonin and dopamine receptors....
bind preferentially to members of the 5-HT2 receptor family.
- KetanserinKetanserinKetanserin is a drug with affinity for multiple G protein-coupled receptors . Initially it was believed to be a highly selective antagonist for serotonin 5-HT2A receptors, however this is not true. Ketanserin only has moderate selectivity for 5-HT2A receptors over 5-HT2C receptors...
, the prototypic 5-HT2 receptor antagonist potently blocks 5-HT2Areceptors, less potently blocks 5-HT2C receptors, and has no significant effect on 5-HT3 or 5-HT4 receptors or any members of the 5-HT1 receptor family. Thus discovery of Ketanserin was a landmark in the pharmacology of 5-HT2 receptors. Ketanserin, though capable of blocking 5-HT induced platelet adhesion, however does not mediate its well known antihypertensive action through 5-HT2 receptor family, but through its high affinity for alpha1 adrenergic receptors. It also has high affinity for H1 histaminergic receptors equal to that at 5-HT2A receptors. Compounds chemically related to ketanserin such as ritanserinRitanserinRitanserin is a serotonin antagonist with possibilities for the treatment of many neurological disorders.When used together with typical antipsychotics in the treatment of schizophrenia is able to decrease negative symptoms and adds some "atypicality" as parkinsonism is slightly decreased.-...
are more selective 5-HT2A receptor antagonists with low affinity for alpha-adrenergic receptors. However, ritanserin, like most other 5-HT2A receptor antagonists, also potently inhibits 5-HT2C receptors.
- NefazodoneNefazodoneNefazodone is an antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity , which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every...
operates by blocking post-synaptic serotonin type-2A receptors and to a lesser extent by inhibiting pre-synaptic serotonin and norepinephrine (noradrenaline) reuptake.
- Atypical antipsychoticAtypical antipsychoticThe atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
drugs like clozapineClozapineClozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
, olanzapineOlanzapineOlanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
, quetiapineQuetiapineQuetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
, risperidoneRisperidoneRisperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
and asenapineAsenapineAsenapine is a new atypical antipsychotic developed for the treatment of schizophrenia and acute mania associated with bipolar disorder by Schering-Plough after its November 19, 2007 merger with Organon International. Development of the drug, through Phase III trials, began while Organon was still...
are relatively potent antagonists of 5-HT2A as are some of the lower potency old generation/typical antipsychotics. Other antagonists are MDL-100,907 (prototype of another new series of 5-HT2Aantagonists) and cyproheptadineCyproheptadineCyproheptadine , sold under the brand name Periactin, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.- Indications :...
.
- PizotifenPizotifenPizotifen or pizotyline , trade name Sandomigran, is a benzocycloheptene based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches.-Uses:...
is a non-selective antagonist.
- 2-alkyl-4-aryl-tetrahydro-pyrimido-azepines are subtype selective antagonists (35g: 60-fold).
- AMDA9-Aminomethyl-9,10-dihydroanthraceneAMDA is an organic compound which acts as a potent and selective antagonist for the 5-HT2A receptor. It has been used to help study the shape of the 5-HT2A protein, and develop a large family of related derivatives with even higher potency and selectivity.- References :...
and related derivatives are another family of selective 5-HT2A antagonists.
- HydroxyzineHydroxyzineHydroxyzine is a first-generation antihistamine of the diphenylmethane and piperazine classes. It was first synthesized by Union Chimique Belge in 1956 and was marketed by Pfizer in the United States later the same year, and is still in widespread use today....
(Atarax)
Inverse agonists
- AC-90179 - potent and selective inverse agonistInverse agonistIn the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
at 5-HT2A, also 5-HT2C antagonist.
- NelotanserinNelotanserinNelotanserin is a drug developed by Arena Pharmaceuticals which acts as an inverse agonist on the serotonin receptor subtype 5-HT2A. APD-125 was shown to be effective and well tolerated in clinical trials, but development was halted in December 2008 because the substance did not meet the trial's...
(APD-125) - selective 5-HT2A inverse agonist developed by Arena PharmaceuticalsArena PharmaceuticalsArena Pharmaceuticals, Inc. is a biopharmaceutical company located in San Diego, California. The company is developing oral medications that target G-protein-coupled receptors. Currently none of the drugs is approved by the U.S...
for the treatment of insomnia. APD-125 was shown to be effective and well tolerated in clinical trials, but development of APD-125 was halted in December 2008 because the substance did not meet the trial's endpoints.
- EplivanserinEplivanserinEplivanserin was an experimental drug for the treatment of insomnia which was being developed by Sanofi Aventis....
(Sanofi Aventis), a sleeping pill that reached phase II trials (but for which the application for approval was withdrawn), acts as a selective 5-HT2A inverse agonist.
- Pimavanserin (ACP-103)PimavanserinPimavanserin is a drug developed by Acadia Pharmaceuticals which acts as an inverse agonist on the serotonin receptor subtype 5-HT2A, with 10x selectivity over 5-HT2C, and no significant affinity or activity at 5-HT2B or dopamine receptors...
- more selective than AC-90179, orally active, antipsychotic in vivo, now in human clinical trials.
- VolinanserinVolinanserinVolinanserin is a highly selective 5-HT2A receptor antagonist. It is widely used in scientific research to investigate the function of the 5-HT2A receptor. Volinanserin is also being trialed as a potential antipsychotic, antidepressant and treatment for insomnia.- References :...
Examples
| Agonist Agonist An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance... s |
Antagonist Receptor antagonist A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses... s |
|---|---|
|
Cyproheptadine Cyproheptadine , sold under the brand name Periactin, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.- Indications :... Ketanserin Ketanserin is a drug with affinity for multiple G protein-coupled receptors . Initially it was believed to be a highly selective antagonist for serotonin 5-HT2A receptors, however this is not true. Ketanserin only has moderate selectivity for 5-HT2A receptors over 5-HT2C receptors... Mirtazapine Mirtazapine is a tetracyclic antidepressant used primarily in the treatment of depression. It is also sometimes used as a hypnotic, antiemetic, and appetite stimulant, and for the treatment of anxiety, among other indications... Nefazodone Nefazodone is an antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity , which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every... Pizotifen Pizotifen or pizotyline , trade name Sandomigran, is a benzocycloheptene based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches.-Uses:... Trazodone Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound... |
Functional selectivity
5-HT2A-receptor ligandsLigand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
may differentially activate the transductional pathways
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
(see above). Studies evaluated the activation of two effectors
Effector (biology)
An effector is a molecule that binds to a protein and thereby alters the activity of that protein...
, PLC
Phospholipase C
Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...
and PLA2
Phospholipase A2
Phospholipases A2 are enzymes that release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids...
, by means of their second messengers. Compounds displaying more pronounced functional selectivity
Functional Selectivity
Functional selectivity is the ligand-dependent selectivity for certain signal transduction pathways in one and the same receptor. This can be present when a receptor has several possible signal transduction pathways...
are 2,5-DMA and 2C-N
2C-N
2C-N, or 2,5-Dimethoxy-4-nitrophenethylamine, is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin.-Chemistry:The full name of the chemical is 2-ethanamine....
. The former induces IP
Inositol triphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate , together with diacylglycerol , is a secondary messenger molecule used in signal transduction and lipid signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell...
accumulation without activating the PLA2 mediated response, while the latter elicits AA
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
release without activating the PLC mediated response.
Recent research has suggested potential signaling differences within the somatosensory cortex between 5-HT2A agonists that produce headshakes in the mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
and those that do not, such as lisuride
Lisuride
Lisuride is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride is described as free base and as hydrogen maleate salt.Lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks...
, as these agents are also non-hallucinogenic in humans despite being active 5-HT2A agonists.
The difference in signal transduction between the two 5-HT2A agonists serotonin and DOI
2,5-Dimethoxy-4-iodoamphetamine
2,5-dimethoxy-4-iodoamphetamine is a psychedelic drug and a substituted amphetamine of the phenethylamine family. It is also a powerful anti-inflammatory that is effective at doses on the order of 100 micrograms in humans, far below its effective dose as a psychedelic. Despite being a substituted...
may be due to the presence of the intracellular proteins called β-arrestin
Arrestin
Arrestins are a small family of proteins important for regulating signal transduction.-Function:Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors in the visual rhodopsin system by Hermann Kühn and co-workers and...
s, more specifically arrestin beta 2
Arrestin beta 2
Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene.Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G protein-coupled receptors and cause specific dampening of...
.
Role of lipophilicity
A set of ligands were evaluated. For agonists, a highly significant linear correlation was observed between binding affinity and lipophilicity. For ligands exhibiting partial agonist or antagonist properties, the lipophilicity was consistently higher than would be expected for an agonist of comparable affinity.Genetics
In humans the gene is located on chromosome 13.
The gene has previously been called just HTR2 until the description of two related genes HTR2B and HTR2C.
Several interesting polymorphism
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
s have been identified for HTR2A:
A-1438G (rs6311
Rs6311
In genetics rs6311 is a gene variation—a single nucleotide polymorphism —in the human HTR2A gene that codes for the 5-HT2A receptor. 5-HT2A is neuroreceptor, and several scientific studies have investigated the effect of the genetic variation on personality, e.g., personality traits measured with...
),
C102T (rs6313
Rs6313
In genetics, rs6313 also called T102C or C102T is a gene variation—a single nucleotide polymorphism —in the human HTR2A gene that codes for the 5-HT2A receptor....
) and
His452Tyr (rs6314
Rs6314
In genetics, rs6314, also called His452Tyr or H452Y, is a gene variation, a single nucleotide polymorphism , in the HTR2A gene that codes for the 5-HT2A receptor....
).
Many more polymorphisms exist for the gene.
A 2006 paper listed 255.
Associations with psychiatric disorders
Several studies have seen links between the -1438G/A polymorphism and mood disorders, such as bipolar disorderBipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
and major depressive disorder.
A weak link with an odds ratio
Odds ratio
The odds ratio is a measure of effect size, describing the strength of association or non-independence between two binary data values. It is used as a descriptive statistic, and plays an important role in logistic regression...
of 1.3 has been found between the T102C polymorphism and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
This polymorphism has also been studied in relation to suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
attempts, with a study finding excess of the C/C genotypes among the suicide attempters. A number of other studies were devoted to finding an association of the gene with schizophrenia, with diverging results.
These individual studies may, however, not give a full picture: A review from 2007 looking at the effect of different SNPs reported in separate studies stated that "genetic association studies [of HTR2A gene variants with psychiatric disorders] report conflicting and generally negative results" with no involvement, small or a not replicated role for the genetic variant of the gene.
Treatment response
One study has found that genetic variations between individuals in the HTR2A gene may to some extent account for the difference in outcome of antidepressant treatment, so that patients suffering from major depressive disorder and treated with CitalopramCitalopram
Citalopram brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor class. It has U.S...
may benefit more than others if they have one particular genotype.
In this study 768 single nucleotide polymorphism
Single nucleotide polymorphism
A single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
(SNP) across 68 genes were investigated and a SNP—termed rs7997012
Rs7997012
In genetics, rs7997012 is a gene variation—a single nucleotide polymorphism —in intron 2 of the human HTR2A gene that codes for the 5-HT2A receptor.The SNP varies between adenine and guanine DNA bases with the G-allele being most frequent....
—in the second intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
of the HTR2A gene showed significant association with treatment outcome.
Genetics seems also to be associated to some extent with the amount of adverse events in treatment of major depression disorder.
Neuroimaging
The 5-HT2A receptors may be imaged with PET-scanners using the fluorine-18-altanserinAltanserin
Altanserin is a compound that binds to the 5-HT2A receptor .It is a yellowish solid.Labeled with the isotope fluorine-18 it is used as a radioligand in positron emission tomography studies of the brain, i.e., studies of the serotonin-2A neuroreceptors.Besides human neuroimaging studies altanserin...
and MDL 100,907
radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....
s that binds to the neuroreceptor, e.g.,
one study reported a reduced binding of altanserin particularly in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
in patients with major depressive disorder.
Another PET study reported increased altanserin binding in the caudate nuclei
Caudate nucleus
The caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:...
in obsessive compulsive disorder patients compared to a healthy control group.
Patients with Tourette's syndrome have also been scanned and the study found an increased binding of altanserin for patients compared to healthy controls. The altanserin uptake decreases with age reflecting a loss of specific 5-HT2A receptors with age.
A study has also found a positive correlation among healthy subjects between altanserin binding and the personality trait neuroticism
Neuroticism
Neuroticism is a fundamental personality trait in the study of psychology. It is an enduring tendency to experience negative emotional states. Individuals who score high on neuroticism are more likely than the average to experience such feelings as anxiety, anger, guilt, and depressed mood...
as measured by the NEO PI-R personality questionnaire.
Role in virus endocytosis
5-HT2A is a necessary receptor for clathrinClathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
mediated endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
of the human polyoma virus called JC virus
JC virus
The JC virus or John Cunningham virus is a type of human polyomavirus and is genetically similar to BK virus and SV40. It was discovered in 1971 and named using the two initials of a patient with progressive multifocal leukoencephalopathy...
, the causative agent of progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy , also known as progressive multifocal leukoencephalitis, is a rare and usually fatal viral disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations .It occurs almost exclusively in...
(PML), that enters cells like oligodendrocyte
Oligodendrocyte
Oligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates...
s, astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s, B lymphocytes, and kidney epithelial cells. These cells need to express both the alpha 2-6–linked sialic acid
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
component of the 5HT2A receptor in order to endocytose JCV.