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32-440: 15550 ENSG00000178394 ENSMUSG00000021721 P08908 Q64264 NM_000524 NM_008308 NP_000515 NP_032334 The serotonin 1A receptor (or 5-HT 1A receptor ) is a subtype of serotonin receptors , or 5-HT receptors, that binds serotonin , also known as 5-HT, a neurotransmitter . 5-HT1A is expressed in the brain , spleen , and neonatal kidney . It is a G protein-coupled receptor (GPCR), coupled to
64-631: A faster onset of action and improved effectiveness compared to those currently available. Unlike most drugs that elevate extracellular serotonin levels like the SSRIs and MAOIs, SRAs such as fenfluramine and MDMA bypass serotonin autoreceptors such as 5-HT 1A . They do this by directly acting on the release mechanisms of serotonin neurons and forcing release to occur regardless of autoreceptor-mediated inhibition. As such, SRAs induce immediate and much greater increases in extracellular serotonin concentrations compared to other serotonin-elevating agents such as
96-871: A group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems . They mediate both excitatory and inhibitory neurotransmission . The serotonin (i.e., 5-hydroxytryptamine, hence "5-HT") receptors are activated by the neurotransmitter serotonin , which acts as their natural ligand . The serotonin receptors modulate the release of many neurotransmitters, including glutamate , GABA , dopamine , epinephrine / norepinephrine , and acetylcholine , as well as many hormones, including oxytocin , prolactin , vasopressin , cortisol , corticotropin , and substance P , among others. Serotonin receptors influence various biological and neurological processes such as aggression, anxiety , appetite, cognition , learning, memory, mood , nausea, sleep, and thermoregulation . They are
128-407: A major mediator in the therapeutic benefits of most mainstream antidepressant supplements and pharmaceuticals , including serotonin precursors like L-tryptophan and 5-HTP , SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), and monoamine oxidase inhibitors (MAOIs). 5-HT 1A receptor activation likely plays
160-560: A major role in its regulation of mood and anxiety. The 5-HT 1A receptor forms heterodimers with the following receptors: 5-HT 7 , 5-HT 1B , 5-HT 1D , GABA B2 , LPA 1 (GPCR26), LPA 3 , S1P 1 , S1P 3 . This article incorporates text from the United States National Library of Medicine , which is in the public domain . Serotonin receptor 5-HT receptors , 5-hydroxytryptamine receptors , or serotonin receptors , are
192-438: A putatively faster onset of action and improved effectiveness compared to current treatments. Similarly to SRAs, sufficiently high doses of 5-HT 1A receptor agonists also bypass the 5-HT 1A autoreceptor-mediated inhibition of serotonin release and therefore increase 5-HT 1A postsynaptic receptor activation by directly agonizing the postsynaptic receptors in lieu of serotonin. The distribution of 5-HT 1A receptors in
224-464: A result, are being developed as novel treatments for Alzheimer's disease . Other effects of 5-HT 1A activation that have been observed in scientific research include: 5-HT 1A receptor activation induces the secretion of various hormones including cortisol , corticosterone , adrenocorticotropic hormone (ACTH), oxytocin , prolactin , growth hormone , and β-endorphin . The receptor does not affect vasopressin or renin secretion, unlike
256-564: A significant role in the positive effects of serotonin releasing agents (SRAs) like MDMA (commonly known as ecstasy) as well. 5-HT 1A receptors in the dorsal raphe nucleus are co-localized with neurokinin 1 (NK 1 ) receptors and have been shown to inhibit the release of substance P , their endogenous ligand . In addition to being antidepressant and anxiolytic in effect, 5-HT 1A receptor activation has also been demonstrated to be antiemetic and analgesic , and all of these properties may be mediated in part or full, depending on
288-404: Is a 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 5A and 5-HT 6 agonist. The genes coding for serotonin receptors are expressed across the mammalian brain. Genes coding for different receptors types follow different developmental curves. Specifically, there is a developmental increase of HTR5A expression in several subregions of the human cortex, paralleled by a decreased expression of HTR1A from
320-675: Is coded by the HTR1A gene . There are several human polymorphisms associated with this gene. A 2007 review listed 27 single nucleotide polymorphisms (SNP). The most investigated SNPs are C-1019G ( rs6295 ), C-1018G, Ile28Val ( rs1799921 ), Arg219Leu ( rs1800044 ), and Gly22Ser ( rs1799920 ). Some of the other SNPs are Pro16Leu, Gly272Asp, and the synonymous polymorphism G294A ( rs6294 ). These gene variants have been studied in relation to psychiatric disorders with no definitive results. The 5-HT 1A receptor has been shown to interact with brain-derived neurotrophic factor (BDNF), which may play
352-425: Is no 5-HT 1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT 2 family of receptors and was redesignated as the 5-HT 2C receptor. Very nonselective agonists of 5-HT receptor subtypes include ergotamine (an antimigraine ), which activates 5-HT 1A , 5-HT 1D , 5-HT 1B , D 2 and norepinephrine receptors . LSD (a psychedelic )
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#1732787453190384-401: Is somewhat reduced with chronic treatment, they still remain effective at constraining large increases in extracellular serotonin concentrations. For this reason, serotonin reuptake inhibitors that also have 5-HT 1A receptor antagonistic or partial agonistic properties, such as vilazodone and SB-649,915 , are being investigated and introduced as novel antidepressants with the potential for
416-463: The 5-HT 2 receptors . It has been suggested that oxytocin release may contribute to the prosocial, antiaggressive , and anxiolytic properties observed upon activation of the receptor. β-Endorphin secretion may contribute to antidepressant, anxiolytic, and analgesic effects. 5-HT 1A receptors can be located on the cell body , dendrites , axons , and both presynaptically and postsynaptically in nerve terminals or synapses . Those located on
448-592: The Edinger-Westphal nucleus , resulting in pupil dilation in rodents , and pupil constriction in primates including humans . 5-HT 1A receptor agonists like buspirone and flesinoxan show efficacy in relieving anxiety and depression . Buspirone and tandospirone are currently approved for these indications in different parts of the world. Others such as gepirone , flesinoxan , flibanserin , and naluzotan have also been investigated, though none have been fully developed and approved yet. Some of
480-571: The Gi protein , and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene . The 5-HT 1A receptor is the most widespread of all the 5-HT receptors. In the central nervous system , 5-HT 1A receptors exist in the cerebral cortex , hippocampus , septum , amygdala , and raphe nucleus in high densities, while low amounts also exist in
512-661: The atypical antipsychotics like lurasidone and aripiprazole are also partial agonists at the 5-HT 1A receptor and are sometimes used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs). Mice lacking 5-HT 1A receptors altogether ( knockout ) show increased anxiety but lower depressive-like behaviour. 5-HT 1A autoreceptor desensitization and increased 5-HT 1A receptor postsynaptic activation via general increases in serotonin levels by serotonin precursor supplementation , serotonin reuptake inhibition , or inhibition of monoamine oxidase has been shown to be
544-412: The basal ganglia and thalamus . The 5-HT 1A receptors in the raphe nucleus are largely somatodendritic autoreceptors , whereas those in other areas such as the hippocampus are postsynaptic receptors. 5-HT 1A receptor agonists are involved in neuromodulation . They decrease blood pressure and heart rate via a central mechanism, by inducing peripheral vasodilation , and by stimulating
576-504: The central and peripheral nervous systems . They can be divided into 7 families of G protein-coupled receptors which activate an intracellular second messenger cascade to produce an excitatory or inhibitory response. The exception to this is the 5-HT 3 receptor which is a ligand-gated ion channel . In 2014, a novel 5-HT receptor was isolated from the small white butterfly, Pieris rapae , and named pr5-HT 8 . It does not occur in mammals and shares relatively low similarity to
608-502: The human brain may be imaged with the positron emission tomography using the radioligand [C] WAY-100,635 . For example, one study has found increased 5-HT 1A binding in type 2 diabetes . Another PET study found a negative correlation between the amount of 5-HT 1A binding in the raphe nuclei , hippocampus and neocortex and a self-reported tendency to have spiritual experiences . Labeled with tritium , WAY-100,635 may also be used in autoradiography . The 5-HT 1A receptor
640-436: The phenylpiperazine class. Originally developed as a potential antihypertensive drug , flesinoxan was later found to possess antidepressant and anxiolytic effects in animal tests. As a result, it was investigated in several small human pilot studies for the treatment of major depressive disorder , and was found to have robust effectiveness and very good tolerability . However, due to "management decisions",
672-468: The skin via central 5-HT 1A activation increases heat dissipation from the organism out into the environment, causing a decrease in body temperature . Activation of central 5-HT 1A receptors triggers the release or inhibition of norepinephrine depending on species, presumably from the locus coeruleus , which then reduces or increases neuronal tone to the iris sphincter muscle by modulation of postsynaptic α 2 -adrenergic receptors within
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#1732787453190704-410: The vagus nerve . These effects are the result of activation of 5-HT 1A receptors within the rostral ventrolateral medulla . The sympatholytic antihypertensive drug urapidil is an α 1 -adrenergic receptor antagonist and 5-HT 1A receptor agonist, and it has been demonstrated that the latter property contributes to its overall therapeutic effects. Vasodilation of the blood vessels in
736-882: The SSRIs. [Note: This is questionable as the level of serotonin output from SRAs is still dose dependant and, while SRAs will initially bypass autoreceptors, the increase in serotonin they induce will then agonise autoreceptors.] In contrast to SRAs, SSRIs may decrease serotonin levels initially (especially at lower dosages due to the biphasic mode of action mentioned above) and require several weeks of chronic dosing before serotonin concentrations reach their maximal elevation (due to 1A autoreceptor desensitization) and full clinical benefits for conditions such as depression and anxiety are seen (although other studies show an acute increase in 5-HT which may account for initial worsening of symptoms in sensitive individuals). For these reasons, selective serotonin releasing agents (SSRAs) such as MDAI and MMAI have been proposed as novel antidepressants with
768-402: The embryonic period to the post-natal one. A number of receptors were classed as "5-HT 1 -like" - by 1998 it was being argued that, since these receptors were "a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7" receptors the classification was redundant. Flesinoxan Flesinoxan ( DU-29,373 ) is a potent and selective 5-HT 1A receptor partial /near- full agonist of
800-592: The known 5-HT receptor classes. The 7 general serotonin receptor classes include a total of 14 known serotonin receptors. The 15th receptor 5-HT 1P has been distinguished on the basis of functional and radioligand binding studies, its existence has never been definitely affirmed or refuted. The specific types have been characterized as follows: [REDACTED] Selective (for 5-HT 1A over other 5-HT receptors) Nonselective [REDACTED] [REDACTED] [REDACTED] Functions in rodents, pseudogene in humans Note that there
832-497: The neuron's release of neurotransmitter inhibits its further release of neurotransmitter. Stimulation of 5-HT 1A autoreceptors inhibits the release of serotonin in nerve terminals. For this reason, 5-HT 1A receptor agonists tend to exert a biphasic mode of action; they decrease serotonin release and postsynaptic 5-HT 1A receptor activity in low doses, and further decrease serotonin release but increase postsynaptic 5-HT 1A receptor activity at higher doses by directly stimulating
864-421: The property in question, by NK 1 receptor inhibition. Consequently, novel NK 1 receptor antagonists are now in use for the treatment of nausea and emesis , and are also being investigated for the treatment of anxiety and depression. 5-HT 1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex , striatum , and hippocampus , and may be useful for improving
896-416: The receptors in place of serotonin. This autoreceptor-mediated inhibition of serotonin release has been theorized to be a major factor in the therapeutic lag that is seen with serotonergic antidepressants such as the SSRIs. The autoreceptors must first desensitize before the concentration of extracellular serotonin in the synapse can become elevated appreciably. Though the responsiveness of the autoreceptors
928-636: The release of glutamate and acetylcholine in various areas of the brain . 5-HT 1A activation is known to improve cognitive functions associated with the prefrontal cortex, possibly via inducing prefrontal cortex dopamine and acetylcholine release. Conversely, the 5-HT 1A antagonist, WAY100635 , alleviated learning and memory impairments induced by glutamate blockade (with dizocilpine ) or hippocampal cholinergic denervation (by fornix transection) in primates. Furthermore, 5-HT 1A receptor antagonists such as lecozotan have been shown to facilitate certain types of learning and memory in rodents, and as
960-404: The soma and dendrites are referred to as somatodendritic , and those located presynaptically in the synapse are simply referred to as presynaptic. As a group, receptors that are sensitive to the neurotransmitter that is released by the neuron on which the receptors are located are known as autoreceptors ; they typically constitute the key component of an ultra-short negative feedback loop whereby
992-655: The symptoms of schizophrenia and Parkinson's disease . As mentioned above, some of the atypical antipsychotics are 5-HT 1A receptor partial agonists, and this property has been shown to enhance their clinical efficacy. Enhancement of dopamine release in these areas may also play a major role in the antidepressant and anxiolytic effects as seen upon postsynaptic activation of the 5-HT 1A receptor. The activation of 5-HT 1A receptors has been demonstrated to impair certain aspects of memory (affecting declarative and non-declarative memory functions) and learning (due to interference with memory-encoding mechanisms), by inhibiting
5-HT1A receptor - Misplaced Pages Continue
1024-495: The target of a variety of pharmaceutical and recreational drugs, including many antidepressants , antipsychotics , anorectics , antiemetics , gastroprokinetic agents , antimigraine agents , hallucinogens , and entactogens . Serotonin receptors are found in almost all animals and are even known to regulate longevity and behavioral aging in the primitive nematode , Caenorhabditis elegans . 5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in
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