Receptors orexin. Medical search. Frequent questions

There were two orexin agonists under development as of 2019[update]. (wikipedia.org)
Several drugs acting on the orexin system are under development, either orexin agonists for the treatment of conditions such as narcolepsy, or orexin antagonists for insomnia. (wikipedia.org)
No neuropeptide agonists are yet available, although synthetic orexin-A polypeptide has been made available as a nasal spray and tested on monkeys. (wikipedia.org)
Most ligands acting on the orexin system so far are polypeptides modified from the endogenous agonists orexin-A and orexin-B, however there are some subtype-selective non-peptide antagonists available for research purposes. (wikipedia.org)
Benzodiazepine receptor agonists are the mainstay in treatment of insomnia. (medscape.com)
Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists. (medchemexpress.com)
While prevailing treatment approaches only address the symptoms associated with narcolepsy type 1 (NT1), we believe orexin agonists offer a disruptive approach, with the capacity to address the underlying pathology of the disorder. (sleepreviewmag.com)
Indeed, the therapeutic possibilities of orexin agonists extend well beyond NT1 into other rare primary hypersomnia disorders, such as narcolepsy type 2 and idiopathic hypersomnia, and into a broad range of additional indications characterized by excessive daytime sleepiness. (sleepreviewmag.com)
We are committed to exploring the full potential of orexin agonists to help patients across a wide range of indications," says Mario Alberto Accardi, PhD, Orexia CEO, in a release. (sleepreviewmag.com)
Benzodiazepine receptor agonists (BZRAs) target a specific part of the brain and may increase a neurotransmitter called gamma-aminobutyric acid (GABA). (medicalnewstoday.com)
These medications are broadly classified as either agonists or antagonists that respectively promote or inhibit receptor activation by endogenous stimuli. (warwick.ac.uk)
The orexin system is an important regulator of the sleep/wake cycle, and small molecule agonists of the orexin receptors could be beneficial for patients suffering from type 1 narcolepsy. (helsinki.fi)
The newer GABA-effective hypnotics are the only medications with demonstrated effectiveness in treating chronic insomnia with the majority of evidence supporting treatment efficacy for cognitive-behavioral therapy and short acting GABA-receptor agonists. (springer.com)

Moreover, orexin neurons, by acting on OxR1 in the LC, play a role in the diurnal gating of REM sleep. (nih.gov)
Histamine-immunoreactive fibers targeted the dorsal telencephalon, an area that expresses histamine receptors hrh1 and hrh3 and contains predominantly glutamatergic neurons. (elsevierpure.com)
The orexins are produced in neurons of the lateral hypothalamic area and implicated in the regulation of both feeding and reproductive function. (elsevierpure.com)
Using double- and triple-label immunofluorescence coupled with confocal microscopy, we found that 75-85% of GnRH neurons were contacted by orexin fibers, and triple labeling with synaptophysin provided additional confirmation of close contacts. (elsevierpure.com)
Furthermore, about 85% of GnRH neurons were colocalized with the orexin receptor 1 (OX-R1), and the OX-R1-expressing GnRH neurons were contacted by orexin terminals, providing the basis for a functional neuroanatomical pathway. (elsevierpure.com)
An additional study investigated the coexpression of neuropeptide Y Y4-like receptors and orexin fibers in relation to GnRH neurons. (elsevierpure.com)
The present study found that, although Y4-positive orexin fibers are in present in the area of GnRH neurons, they never come in close contact with GnRH neurons. (elsevierpure.com)
Together, these data suggest that Y4 receptor modulation of LH release is likely to be indirect through orexin cell bodies and that orexin modulates GnRH neurons directly via OX-R1. (elsevierpure.com)
Both orexin-A and orexin-B depolarized the histaminergic tuberomammillary neurons and increased their firing rate via an action on postsynaptic receptors. (jneurosci.org)
In a single-cell RT-PCR study using primers for the two orexin receptors, we found that most tuberomammillary neurons express both receptors and that the expression of the orexin-2 receptor is stronger than that of the orexin-1 receptor. (jneurosci.org)
Immunocytochemical studies show that the histamine and orexin neurons are often located very close to each other. (jneurosci.org)
The contacts between these two types of neurons seem to be reciprocal, because the orexin neurons are heavily innervated by histaminergic axons. (jneurosci.org)
Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functions via modulation of the hypothalamic-pituitary-gonadal axis. (researchgate.net)
We suggested a pivotal role for endocannabinoids in food reward processing within the lateral hypothalamus, and for orexin neurons to integrate endocrine signals with food reinforcement and hedonic eating. (frontiersin.org)
In addition, the role played by different stressors in the reinstatement of preference for palatable food and food-seeking behavior is also considered in the light of endocannabinoid production, activation of orexin receptors and disinhibition of dopamine neurons. (frontiersin.org)
Hypocretin/orexin (HCRT) neurons provide excitatory input to wake-promoting brain regions including the basal forebrain (BF). (sri.com)
Orexin interacts with several wake-promoting neuronal groups, such as the histaminergic neurons of the tuberomammilary nucleus and the noradrenergic neurons of the locus coeruleus. (proteopedia.org)
Therefore, it can be concluded that when Orexin neurons are stimulated the possibility of transitioning to a state of wakefulness increases. (proteopedia.org)
However, if Orexin neurons are inhibited the probability of transitioning to sleeping state increases. (proteopedia.org)
5 The anorexigenic effect of monoamine serotonin is also mediated by the 5HT-2C receptor in POMC neurons. (nature.com)

The hypothalamic orexin (hypocretin) neuropeptides are associated with the regulation of sleep and feeding, and disturbances in orexinergic neurotransmission lead to a narcoleptic phenotype. (jneurosci.org)
Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. (researchgate.net)
Hypocretins, also called Orexins, are hypothalamic neuropeptides that serve important functions in the regulation of an individual's sleep/wake cycle, homeostatic systems such as thermoregulation, appetite, and reward processing [1] . (proteopedia.org)
Blocking the binding of wake-promoting neuropeptides orexin to receptors OX1R and OX2R is thought to suppress wake drive (Ki values of 8.1 nM and 0.48 nM, respectively). (eisai.com)

Both orexin receptors exhibit a similar pharmacology - the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. (wikipedia.org)
Orexin 2 Receptor Agonist is a potent selective OX2R agonist with an EC 50 of 23 nM. (medchemexpress.com)
Orexin 2 Receptor Agonist replaces Orexin-A to bind to hOX1R and hOX2R in a concentration-dependent manner in CHO cells overexpressing hOX1R and HEK-293 cells overexpressing hOX2R with K i values of 0.14 μM and 0.77 μM, respectively [1] . (medchemexpress.com)
The collaboration represents the first time Schrödinger's technology will be applied in an orexin agonist setting at scale. (sleepreviewmag.com)
[ 17 ] and a short course of a sedative-hypnotic or melatonin receptor agonist. (medscape.com)
Yoshioka R, Yamamoto S, Nakatani E, Yasui-Furukori N. Effectiveness of suvorexant versus benzodiazepine receptor agonist sleep drugs in reducing the risk of hip fracture: Findings from a regional population-based cohort study. (jmir.org)
Bhyrapuneni G, Benade V, Daripelli S, Kamuju V, Shinde A, Abraham R, Nirogi R, Jasti V (2019) SUVN-G3031, histamine H3 receptor inverse agonist preclinical evaluation for the treatment of excessive daytime sleepiness in narcolepsy. (atsbio.com)
SUVN-G3031, a potent histamine H3 receptor inverse agonist is being developed for the treatment of narcolepsy and other sleep related disorders. (atsbio.com)
Evidence for an excitatory action of benzodiazepine receptor inverse agonist FG 7142 on C-fibre afferents. (rndsystems.com)
In January 2014, the FDA approved the melatonin receptor agonist tasimelteon (Hetlioz) as the first treatment for non-24- hour sleep-wake disorder ("non-24"), a chronic circadian disorder that affects the timing of sleep, in individuals who are completely blind. (medscape.com)

Schrödinger and Centessa Pharmaceuticals plc, together with subsidiary Orexia Therapeutics, have entered into an exclusive collaboration focused on the discovery of novel therapeutics targeting the orexin-2 receptor (OX2R), which is known to play a role in a broad spectrum of sleep disorders, including narcolepsy. (sleepreviewmag.com)
Orexia's utilization of OX2R stabilized receptors (StaR technology) provides the foundation for R&D which could significantly benefit patients with NT1. (sleepreviewmag.com)
Orexin-A can be described as a non-subtype-selective neuropeptide that is capable of binding to either OX1R and OX2R, the two possible Orexin receptors, with roughly equal affinities. (proteopedia.org)
However, Orexin-B binds to OX2R with an affinity 10 times greater than its affinity for OX1R [2] . (proteopedia.org)
Although the structures of the N-terminal α-helixes of both OX1R and OX2R are similar, the orientation varies between the two receptors. (proteopedia.org)
Low amounts of Orexin and mutations of the OX2R gene (HCRTR2) have been linked to the development of narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. (proteopedia.org)
DAYVIGO is a dual orexin receptor antagonist that inhibits orexin neurotransmission regulating sleep-wake rhythm by binding competitively to the two subtypes of orexin receptors (OX1R and OX2R). (eisai.com)
DAYVIGO binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist with stronger inhibition effect on OX2R, which suppresses both REM and non-REM sleep drive, such that DAYVIGO may provide faster sleep onset and better sleep maintenance to patients. (eisai.com)
DAYVIGO is Eisai's in-house discovered and developed small molecule that binds to orexin receptors, OX1R and OX2R, and acts as a competitive antagonist (IC 50 values of 6.1 nM and 2.6 nM, respectively). (eisai.com)

We sought to assess one such function known to be susceptible to basal forebrain cholinergic manipulation, olfactory discrimination acquisition, and reversal learning, in rats following intra-basal forebrain infusion of OxA or the orexin 1 receptor (OxR1) antagonist SB-334867. (ox.ac.uk)
We examined the involvement of the orexin system in cue-induced reinstatement of extinguished cocaine-seeking by administering the orexin 1 receptor antagonist SB-334867 (SB) or the orexin 2 receptor antagonist 4-pyridylmethyl (S)-tert-leucyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (4PT) prior to reinstatement testing. (tamu.edu)

Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. (springer.com)
Trajanović N. Dual orexin receptor antagonist in treatment of insomnia. (jmir.org)
The mechanism of action of DAYVIGO in the treatment of insomnia is presumed to be through antagonism of orexin receptors. (eisai.com)
Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant. (nih.gov)

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") announced today that its Hong Kong subsidiary Eisai (Hong Kong) Co., Ltd. has obtained approval for the in-house-discovered and developed orexin receptor antagonist DAYVIGO ® (generic name: lemborexant) for the treatment of adults with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. (eisai.com)
Increased plasma orexin-A levels in patients with insomnia disorder are not associated with prepro-orexin or orexin receptor gene polymorphisms. (cdc.gov)

The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. (wikipedia.org)
The OX 2 receptors , also known as hypocretin receptor 2, are located primarily in the cerebral cortex, paraventricular hypothalamus, nucleus accumbens, subthalamic and paraventricular thalamus where they are thought to regulate sleep-wakefulness. (tocris.com)

The N-terminal α-helixes serve a critical roll in Orexin-A-mediated neuropeptide activation. (proteopedia.org)
The orexin neuropeptide signaling system plays a role in wakefulness. (eisai.com)

and the orexin peptides have been implicated in physiological roles similar to those of HA. (jneurosci.org)
Both Orexin-peptides consist of two amphipathic α-helixes, which have similar properties to the N-terminal α-helixes found on Orexin receptors. (proteopedia.org)
To develop new therapeutics, understanding the interactions between the orexin peptides and their cognate receptors is crucial. (helsinki.fi)

These drugs bind to a special benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex, enhancing the activity of this neurotransmitter. (medscape.com)
The histaminergic and hypocretin/orexin (hcrt) neurotransmitter systems play crucial roles in alertness/wakefulness in rodents. (elsevierpure.com)
The newest class of sleeping pills, orexin receptor antagonists inhibit orexin, a neurotransmitter in the brain that promotes wakefulness. (sleepreviewmag.com)
DAYVIGO acts on the orexin neurotransmitter system and is believed to facilitate sleep onset, sleep maintenance, and wake by regulating sleep-wake rhythm. (eisai.com)

Orexins stimulate LH secretion in steroid-primed ovariectomized female rats and suppress LH secretion in nonprimed ovariectomized rats. (elsevierpure.com)

Zolpidem binds at a benzodiazepine receptor subtype (omega I). This receptor is found more in the central nervous system (CNS) than in the peripheral nervous system, which helps to account for the drug's hypnotic effect without significant muscle-relaxant properties. (medscape.com)

WRAP-A-novel-phosphorylation-site-orexin-receptor-1-regulating-Chen-2020.pdf - Accepted Version - Requires a PDF viewer. (warwick.ac.uk)
VSI: Orexin/Hypocretin Beijing: Medicine in Drug Discovery/Elsevier, 2020. (usd.edu)

precursor, prepro-orexin (PPO). (researchgate.net)

The OX 2 receptor displays equal affinity for Orexin A and Orexin B. The human OX 2 receptor gene has been localized to chromosome 6 (6p11-q11). (tocris.com)
Suvorexant is a highly selective reversible high affinity orexin receptor antagonist. (tga.gov.au)
Higher affinity and faster on/off receptor kinetics of DAYVIGO to orexin receptor 2, which also suppresses non-REM sleep, indicates its potential to facilitate non-sedative onset and maintenance of sleep. (eisai.com)

It interacts with the GABA-benzodiazepine receptor complex, causing sedation. (medscape.com)

The dual HCRT receptor antagonist almorexant (ALM) decreases waking and increases sleep. (sri.com)

Orexin receptors produce neuroexcitation through postsynaptic depolarization by activating non-selective cation channels, inhibiting K+ channels, and activating Na+/Ca2+ exchange. (proteopedia.org)
SB 334867 is a selective non-peptide orexin OX 1 receptor antagonist. (tocris.com)
Nonpeptide OX1 selective antagonist with >100 fold selectivity over the OX2 receptor. (axonmedchem.com)

However, orexin-B shows a 5- to 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors. (wikipedia.org)

There is evidence that Y4 receptor stimulation results in LH release, and studies from our laboratory show Y4-like immunoreactivity in the majority of orexin cell bodies in the lateral hypothalamic area and some orexin fibers scattered throughout the hypothalamus. (elsevierpure.com)
Thus, the lateral hypothalamus-ventral tegmental area-nucleus accumbens neural circuitry is reexamined in order to interrogate the functional interplay between ghrelin, dopamine, orexin, and endocannabinoid signaling. (frontiersin.org)
Finally, type-1 cannabinoid receptor-dependent inhibition of GABA-ergic release and relapse to reward-associated stimuli is linked to ghrelin and orexin signaling in the lateral hypothalamus-ventral tegmental area-nucleus accumbens network to highlight its pathological potential for food addiction-like behavior. (frontiersin.org)
Therefore, the anorexigenic effect exerted by the CBD could be the result of a multitarget mechanism, involving the whole endocannabinoid receptor system, particularly in the hypothalamus. (researchgate.net)
Nevertheless, the study performed by Merroun and colleagues [33] suggested the lateral hypothalamus-derived orexin A as a mediator of the anorexigenic effects induced by CB1 antagonist AM251 as well [33]. (researchgate.net)

The aim of the present study was to characterize the neuroanatomical pathway by which orexin might modulate LH secretion in the rat. (elsevierpure.com)

Suvorexant is in a class of medications called orexin receptor antagonists. (medlineplus.gov)

The primary function of the orexin system, i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. (researchgate.net)

In Orexin/Hypocretin 21 Years On: Pharmacology, Physiology and Drug Discovery , 1-20. (usd.edu)

Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. (researchgate.net)
Fragmented sleep is caused by the instability of behavioral state regulation due to the lack of Orexin lowering the thresholds required to transition between sleep and wakefulness. (proteopedia.org)

In the new study, the research team used a massive gene-screening technique to identify genes that orexin either turned on or inhibited. (medindia.net)

The orexin system, which influences motivated and addictive behaviors through the peptide orexin, may underly the relationship: orexin activity increases during sleep deprivation, and blocking orexin receptors reduces reward-seeking. (sciencedaily.com)

Lemborexant, an orexin receptor antagonist, was approved for use in the United States in 2019. (wikipedia.org)

Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking. (tamu.edu)

Orexin receptor activity in the basal forebrain alters performance on an olfactory discrimination task. (ox.ac.uk)
These data suggest that orexin acting in the basal forebrain may be important for cortical-dependant executive functions, possibly through the stimulation of cortical ACh release. (ox.ac.uk)

Translation inhibition of histidine decarboxylase (hdc) with morpholino oligonucleotides (MOs) led to a behaviorally measurable decline in light-associated activity, which was partially rescued by hdc mRNA injections and mimicked by histamine receptor H1 (Hrh1) antagonist pyrilamine treatment. (elsevierpure.com)

Finally, our data shows that the hydrophobic side of helix 1 of the amphipathic orexin-A should be seriously considered in the analysis of binding modes. (helsinki.fi)

Orexin receptor 1 (OX1R), a member of the GPCRs, is an important drug target in the central nervous system. (warwick.ac.uk)
The orexin/hypocretin system has recently been implicated in reward-processing and addiction. (tamu.edu)
whereas a disrupted orexin system leads to narcolepsy. (jneurosci.org)
Research in the MPL focuses on the role of the brain's (pro)renin receptor (PRR) and other members of the renin angiotensin system in the development of hypertension, metabolic syndrome, and heart failure. (mtu.edu)
Blocking the orexin system reduced the increased cocaine preference driven by sleep deprivation. (sciencedaily.com)

3 Dual orexin receptor antagonists (DORA), a new class of hypnotics, were recently marketed with precautionary measures for use in patients with MDD and suicidal ideation. (psychiatrist.com)

Drug discovery efforts targeting G protein-coupled receptors (GPCRs) have succeeded in developing multiple medications for treating various human diseases including cancer, metabolic disorders, and inflammatory disorders. (warwick.ac.uk)

These target and activate the GABA receptors in the brain, which promote sleepiness, she says. (sleepreviewmag.com)

Here, we identify structurally conserved regions at the predicted binding site and conserved residues of the orexin-A peptide by comparing orexin 2 receptor sequences from nine diverse species as well as with insect allatotropin receptor, a distant relative, and orexin-A sequences from 10 different species. (helsinki.fi)
Conservation in orexin-A is concentrated on the C-terminus, while the most conserved individual residues of the peptide are L20, G29, I30, and L31. (helsinki.fi)
Applying our conservation results into the analysis of two previously suggested binding modes for orexin-A shows that one of the two demonstrates better mirroring of the conserved residues between the peptide and the binding site. (helsinki.fi)

Anatomy12

Organisms3

Diseases4

Chemicals and Drugs21

Analytical, Diagnostic and Therapeutic Techniques and Equipment6

Psychiatry and Psychology15

Phenomena and Processes12

Disciplines and Occupations1

Agonists13

Neurons20

Neuropeptides4

Agonist10

OX2R9

Antagonist SB-3348672

Treatment of insomnia4

Insomnia2

Hypocretin receptor2

Neuropeptide2

Peptides3

Neurotransmitter4

Rats1

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Prepro-orexin1

Affinity3

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Hcrt1

Selective3

Selectivity1

Hypothalamus5

Modulate1

Suvorexant1

Neuronal1

Pharmacology1

Regulation2

Gene1

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Basal Forebrain2

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System5

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GPCRs1

GABA1

Residues3