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https://www.readbyqxmd.com/read/28631980/orexin-research-patent-news-from-2016
#1
Christoph Boss, Catherine Roch
The orexin (hypocretin) system consists of two G-protein-coupled receptors, orexin 1 (Ox1) and orexin 2 (Ox2) and two endogenous peptidic ligands, orexin A (OxA) and orexin B (OxB). It is evolutionarily highly conserved. In the brain, it is involved in the promotion of wakefulness under motivational circumstances as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists (DORAs) such as suvorexant are successfully used to treat primary insomnia...
June 20, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28609741/electrocatalytic-activity-of-manganese-oxide-nanosphere-immobilized-onto-deoxyribonucleic-acid-modified-electrode-application-to-determine-environmental-pollutant-thiourea-at-natural-ph
#2
Afshin Maleki, Hiua Daraei, Nader Amini
Based on immobilizing manganese oxide nanospheres (MnOxNsph)/deoxyribonucleic (DNA) on glassy carbon electrode (MnOxNsph/DNA/GCE), a new electrochemical biosensor for the detection of thiourea (TU) was fabricated. In order to prepare DNA template, cyclic voltammetry (CV) method was used. Scanning electron microscopy (SEM) was used for characterization of MnOx/DNA. Electrochemical impedance spectroscopy was utilized to confirm the successful stepwise assembly procedure of the biosensor. The electrocatalytical behaviors of the biosensor were also investigated by cyclic voltammetry and differential pulse voltammetry (DPV)...
June 7, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28575023/orexin-receptor-agonist-yan-7874-is-a-weak-agonist-of-orexin-hypocretin-receptors-and-shows-orexin-receptor-independent-cytotoxicity
#3
Ainoleena Turku, Maiju K Rinne, Gustav Boije Af Gennäs, Henri Xhaard, Dan Lindholm, Jyrki P Kukkonen
Two promising lead structures of small molecular orexin receptor agonist have been reported, but without detailed analyses of the pharmacological properties. One of them, 1-(3,4-dichlorophenyl)-2-[2-imino-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl]ethan-1-ol (Yan 7874), is commercially available, and we set out to analyze its properties. As test system we utilized human OX1 and OX2 orexin receptor-expressing Chinese hamster ovary (CHO) K1 cells as well as control CHO-K1 and neuro-2a neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28495313/posterior-hypothalamus-glutamate-infusion-decreases-pentylenetetrazol-induced-seizures-of-male-rats-through-hippocampal-histamine-increase
#4
Atieh Arzhang, Mahmoud Elahdadi Salmani, Taghi Lashkarbolouki, Iran Goudarzi
OBJECTIVES: Seizures are epileptic manifestations that are intrinsically modulated through different neurotransmitters and receptor systems. Although glutamate increases excitation and hence seizures, it activates other systems which could potentially terminate seizures. Histamine originates from neurons of the posterior hypothalamus (PH) and can mediate anticonvulsant properties, but the effect of local PH glutamate on hippocampal histamine content is unknown. Therefore, in this study, the effect of PH glutamate and the involvement of hippocampal histamine in pentylenetetrazol (PTZ) induced seizure activity was studied...
July 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28442349/perinatal-programming-of-the-orexinergic-hypocretinergic-system-in-hypothalamus-and-anterior-pituitary-by-testosterone
#5
Natalia I Cataldi, Victoria A Lux-Lantos, Carlos Libertun
Orexins A/B derived from hypothalamic prepro-orexin (PPO) are agonists for orexin receptors 1 (OX1) and 2 (OX2). Previously, we showed clear sex differences in the hypothalamic-pituitary-gonadal orexinergic system in adult rodents. Here, we studied the effect of sexual brain differentiation on the orexinergic system in neuroendocrine structures regulating reproduction. We evaluated: a: proestrous and neonatally androgenized female rats; b: adult males, untreated or gonadectomized in adulthood and injected with oil or estradiol and progesterone (E2/P4); c: control and demasculinized males (perinatally treated with flutamide and later castration) injected either with oil or E2/P4 in adulthood...
April 22, 2017: Peptides
https://www.readbyqxmd.com/read/28389870/orexin-directly-enhances-the-excitability-of-globus-pallidus-internus-neurons-in-rat-by-co-activating-ox1-and-ox2-receptors
#6
He-Ren Gao, Qian-Xing Zhuang, Yong-Xiao Zhang, Zhang-Peng Chen, Bin Li, Xiao-Yang Zhang, Yi-Ting Zhong, Jian-Jun Wang, Jing-Ning Zhu
Orexin, released from the hypothalamus, has been implicated in various basic non-somatic functions including feeding, the sleep-wakefulness cycle, emotion, and cognition. However, the role of orexin in somatic motor control is still little known. Here, using whole-cell patch clamp recording and immunostaining, we investigated the effect and the underlying receptor mechanism of orexin-A on neurons in the globus pallidus internus (GPi), a critical structure in the basal ganglia and an effective target for deep brain stimulation therapy...
April 7, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28296947/the-dual-orexin-receptor-antagonist-tcs1102-does-not-affect-reinstatement-of-nicotine-seeking
#7
Shaun Yon-Seng Khoo, Gavan P McNally, Kelly J Clemens
The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OX1 and OX2 receptors individually have been shown to influence nicotine self-administration and reinstatement. Due to the increasing clinical use of dual orexin receptor antagonists in the treatment of disorders such as insomnia, we examined whether a dual orexin receptor antagonist may also be effective in reducing nicotine seeking. We tested the effect of intracerebroventricular (i...
2017: PloS One
https://www.readbyqxmd.com/read/28274803/the-effect-of-orexin-1-and-orexin-2-receptors-antagonisms-in-the-basolateral-amygdala-on-memory-processing-in-a-passive-avoidance-task
#8
Motahareh Rouhi Ardeshiri, Narges Hosseinmardi, Esmaeil Akbari
There is an extensive evidence concerning basolateral amygdala (BLA) function to hippocampal memory processing. However, few researches have addressed the orexinergic system roles in this modulation. Then, the present study aims at investigating the action of orexin 1 and 2 receptors in BLA on passive avoidance (PA) learning. Wistar male rats (n=79) were trained to avoid foot shock in one type of PA task. The rats were injected bilaterally into BLA, a selective orexin 1 receptor antagonist, SB-334867-A (3, 6, 12μg/0...
March 6, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28181310/localization-of-orexin-b-and-receptor-2-for-orexins-in-testicular-cytotypes-of-the-camelid-alpaca-vicugna-pacos
#9
G Liguori, C Squillacioti, L Assisi, N Mirabella, E Langella, A Costagliola, A Vittoria
The orexins A (OxA) and B (OxB) are two hypothalamic peptides involved in many physiological functions of the mammalian body. They act through the binding of two G-coupled receptors named receptor 1 (OX1 ) and receptor 2 (OX2 ) for orexins. The first receptor is specific for OxA, while the second binds both the substances with equal affinity. The orexins and the relative receptors have been traced by means of different techniques also at the periphery of the body and particularly in the adrenals, and in gastrointestinal and genital organs...
June 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28145492/hypocretin-orexin-peptides-excite-rat-neuroendocrine-dopamine-neurons-through-orexin-2-receptor-mediated-activation-of-a-mixed-cation-current
#10
David J Lyons, Arash Hellysaz, Rachida Ammari, Christian Broberger
Hypocretin/Orexin (H/O) neurons of the lateral hypothalamus are compelling modulator candidates for the chronobiology of neuroendocrine output and, as a consequence, hormone release from the anterior pituitary. Here we investigate the effects of H/O peptides upon tuberoinfundibular dopamine (TIDA) neurons - cells which control, via inhibition, the pituitary secretion of prolactin. In whole cell recordings performed in male rat hypothalamic slices, application of H/O-A, as well as H/O-B, excited oscillating TIDA neurons, inducing a reversible depolarising switch from phasic to tonic discharge...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28041630/the-analgesic-effect-of-orexin-a-in-a-murine-model-of-chemotherapy-induced-neuropathic-pain
#11
Satoshi Toyama, Naohito Shimoyama, Megumi Shimoyama
Orexins are neuropeptides that are localized to neurons in the lateral and dorsal hypothalamus but its receptors are distributed to many different regions of the central nervous system. Orexins are implicated in a variety of physiological functions including sleep regulation, energy homeostats, and stress reactions. Furthermore, orexins administered exogenously have been shown to have analgesic effects in animal models. A type of intractable pain in patients is pain due to chemotherapy-induced peripheral neuropathy (CIPN)...
February 2017: Neuropeptides
https://www.readbyqxmd.com/read/27925365/regenerative-electroless-etching-of-silicon
#12
Kurt W Kolasinski, Nathan J Gimbar, Haibo Yu, Mark Aindow, Ermei Mäkilä, Jarno Salonen
Regenerative electroless etching (ReEtching), described herein for the first time, is a method of producing nanostructured semiconductors in which an oxidant (Ox1 ) is used as a catalytic agent to facilitate the reaction between a semiconductor and a second oxidant (Ox2 ) that would be unreactive in the primary reaction. Ox2 is used to regenerate Ox1 , which is capable of initiating etching by injecting holes into the semiconductor valence band. Therefore, the extent of reaction is controlled by the amount of Ox2 added, and the rate of reaction is controlled by the injection rate of Ox2 ...
January 9, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27909990/orexin-hypocretin-signaling
#13
Jyrki P Kukkonen
Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX1 and OX2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling...
2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909987/orexin-ox2-receptor-antagonists-as-sleep-aids
#14
Laura H Jacobson, Sui Chen, Sanjida Mir, Daniel Hoyer
The discovery of the orexin system represents the single major progress in the sleep field of the last three to four decades. The two orexin peptides and their two receptors play a major role in arousal and sleep/wake cycles. Defects in the orexin system lead to narcolepsy with cataplexy in humans and dogs and can be experimentally reproduced in rodents. At least six orexin receptor antagonists have reached Phase II or Phase III clinical trials in insomnia, five of which are dual orexin receptor antagonists (DORAs) that target both OX1 and OX2 receptors (OX2Rs)...
2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27906750/role-of-orexin-2-and-cb1-receptors-within-the-periaqueductal-gray-matter-in-lateral-hypothalamic-induced-antinociception-in-rats
#15
Mohammad-Hossein Esmaeili, Zahra Reisi, Somayeh Ezzatpanah, Abbas Haghparast
Orexin plays an important role in pain modulation. Orexin-1 and orexin-2 receptors (Ox1r and Ox2r) are found at high density in the ventrolateral periaqueductal gray matter (vlPAG). Our previous study showed that chemical stimulation of the lateral hypothalamus with carbachol induces antinociception in the tail-flick test, a model of acute pain, and Ox1r-mediated antinociception in the vlPAG is modulated by the activity of vlPAG CB1 receptors. In the current study, TCS OX2 29, an Ox2r antagonist (5, 15, 50, 150, and 500 nmol/l), was microinjected into the vlPAG 5 min before the administration of carbachol (125 nmol/l)...
November 30, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27739093/sb-334867-an-orexin-receptor-1-antagonist-decreased-seizure-and-anxiety-in-pentylenetetrazol-kindled-rats
#16
Elham Kordi Jaz, Ali Moghimi, Masoud Fereidoni, Saeedeh Asadi, Ali Shamsizadeh, Ali Roohbakhsh
Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol (PTZ)-kindled rats...
April 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27683906/hypocretin-orexin-peptides-alter-spike-encoding-by-serotonergic-dorsal-raphe-neurons-through-two-distinct-mechanisms-that-increase-the-late-afterhyperpolarization
#17
Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N Ross, Christopher S Leonard
UNLABELLED: Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), but was not blocked by UCL2077, an antagonist of sAHPs in some neurons...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27625592/nucleus-accumbens-shell-and-mpfc-but-not-insula-orexin-1-receptors-promote-excessive-alcohol-drinking
#18
Kelly Lei, Scott A Wegner, Ji Hwan Yu, Arisa Mototake, Bing Hu, Frederic W Hopf
Addiction to alcohol remains a major social and economic problem, in part because of the high motivation for alcohol that humans exhibit and the hazardous binge intake this promotes. Orexin-1-type receptors (OX1Rs) promote reward intake under conditions of strong drives for reward, including excessive alcohol intake. While systemic modulation of OX1Rs can alter alcohol drinking, the brain regions that mediate this OX1R enhancement of excessive drinking remain unknown. Given the importance of the nucleus accumbens (NAc) and anterior insular cortex (aINS) in driving many addictive behaviors, including OX1Rs within these regions, we examined the importance of OX1Rs in these regions on excessive alcohol drinking in C57BL/6 mice during limited-access alcohol drinking in the dark cycle...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27546834/pharmacophore-model-to-discover-ox1-and-ox2-orexin-receptor-ligands
#19
Ainoleena Turku, Alexandre Borrel, Teppo O Leino, Lasse Karhu, Jyrki P Kukkonen, Henri Xhaard
Small molecule agonists and antagonists of the orexinergic system have key implications for research and therapeutic purposes. We report a pharmacophore model trained on ∼200 antagonists and prospectively validated by screening a collection of ∼137,000 compounds. The resulting hit list, 395 compounds, was tested for OX1 and OX2 receptor activity using calcium mobilization assay in recombinant cell lines. Validation was conducted using both calcium mobilization and [(125)I]-orexin-A competition binding. Compounds 4-7 have weak agonist activity and Ki's in the 1-30 μM range; compounds 8-14 are antagonists with Ki's in the 0...
September 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27523303/orexin-1-receptor-blockade-suppresses-compulsive-like-alcohol-drinking-in-mice
#20
Kelly Lei, Scott A Wegner, Ji-Hwan Yu, F Woodward Hopf
Addiction is promoted by pathological motivation for addictive substances, and, despite extensive efforts, alcohol use disorders (AUDs) continue to extract a very high social, physical, and economic toll. Compulsive drinking of alcohol, where consumption persists even when alcohol is paired with negative consequences, is considered a particular obstacle for treating AUDs. Aversion-resistant alcohol intake in rodents, e.g. where rodents drink even when alcohol is paired with the bitter tastant quinine, has been considered to model some compulsive aspects of human alcohol consumption...
November 2016: Neuropharmacology
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