المؤلفون: Schele, Erik, Stoltenborg, Iris, Xie, Anders, 1997, Peris-Sampedro, Fiona, Adan, R. A. H., Dickson, Suzanne L., 1966

المصدر: European Neuropsychopharmacology. 70:63-71

مصطلحات موضوعية: Neurosciences, Neurovetenskaper, Orexin, Anorexia nervosa, Suvorexant, Activity-based anorexia model, food-anticipatory activity, lateral hypothalamus, physical-activity, sleep, neurons, narcolepsy, nervosa, suvorexant, receptor-2, expression, Neurosciences & Neurology, Pharmacology & Pharmacy, Psychiatry

الوصف: While excessive physical activity is common amongst anorexia nervosa (AN) patients, contributing to their low body weight, little is known about the underlying biology and effective treatments targeting the hyperactivity are lacking. Given the role of orexin in arousal, physical activity and energy expenditure, we sought to investigate i) the extent to which orexin neurons are activated during severe anorectic state in the activity-based anorexia (ABA) mouse model, and ii) if the dual orexin receptor antagonist suvorexant can reduce physical activity during ABA. The Fos-TRAP2 technique enable us to visually capture active neurons (Fos expressing) during severe anorectic state in the ABA mouse model, and by immunohistochemistry, determine the extent to which these active neurons are orexin positive. In addition, suvorexant was administered peripherally to ABA mice and running activity was monitored. We found that a large population of orexin neurons in the hypothalamus are activated by ABA and that peripheral administration of suvorexant decreases food anticipatory activity in these mice. We conclude that orexin may be a suitable target to treat hyperactivity in AN and recommend further studies to examine the efficacy of suvorexant in aiding AN patients to control their drive for hyperactivity. (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0Test/)

الوصول الحر: https://gup.ub.gu.se/publication/326252Test

المؤلفون: Rüdiger Kornberger, Benjamin Berger, Jasper Dingemanse

المصدر: European Neuropsychopharmacology. 51:90-104

مصطلحات موضوعية: Pyrrolidines, Visual analogue scale, Citalopram, Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Pharmacokinetics, mental disorders, Humans, Medicine, Single-Blind Method, Pharmacology (medical), Biological Psychiatry, business.industry, Imidazoles, Antagonist, Healthy Volunteers, Orexin receptor, 030227 psychiatry, Psychiatry and Mental health, Neurology, Tolerability, Pharmacodynamics, Orexin Receptor Antagonists, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Blood sampling

الوصف: Daridorexant (ACT-541468) is a new dual orexin receptor antagonist being evaluated for the treatment of insomnia, which is a common comorbidity of depression and anxiety. Therefore, daridorexant is likely to be administered concomitantly with agents (e.g., citalopram) used to treat these disorders. In this single-centre, single-blind, randomized, placebo-controlled, sequential design Phase 1 study with the inclusion of two double-blind crossover parts, the pharmacokinetic (PK; blood sampling at regular intervals) and pharmacodynamic (PD; battery of objective and subjective PD tests performed at regular intervals) interactions between daridorexant (50 mg) and citalopram (20 mg, single dose and at steady state) as well as the safety/tolerability in healthy subjects were investigated. There were no relevant effects of citalopram (single dose/steady state) on daridorexant exposure and vice versa. PD variables measured after morning administration of daridorexant alone showed effects consistent with a sleep-promoting compound. Only co-administration of daridorexant with citalopram at steady state led to relevant changes in objective (unstable tracking) and subjective (visual analogue scale alertness and Karolinska Sleepiness Scale) PD endpoints compared to daridorexant alone. No serious or severe adverse events were reported, while no clinically relevant treatment-emergent effects on ECG parameters, clinical laboratory, or vital signs were observed. In conclusion, the co-administration of daridorexant and citalopram lead to only minor changes in PK parameters, while performance of PD assessments following co-administration were mainly driven by the expected central nervous system effects of daridorexant. Doses up to 50 mg daridorexant can be safely co-administered with citalopram.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd9f9245670717330f545cd9619d54e6Test
https://doi.org/10.1016/j.euroneuro.2021.05.005Test

المؤلفون: Shole Jamali, Abbas Haghparast

المصدر: European Neuropsychopharmacology. 40:S18-S19

مصطلحات موضوعية: Pharmacology, Biology, Conditioned place preference, Orexin, Psychiatry and Mental health, Neurology, Expression (architecture), Morphine, medicine, Pharmacology (medical), Neurology (clinical), Receptor, Prefrontal cortex, Neuroscience, Biological Psychiatry, medicine.drug

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::3cc9f76e16b94d59f7fe503eb3e07cc3Test
https://doi.org/10.1016/j.euroneuro.2020.09.030Test

المؤلفون: D. Kelsh, Jasper Dingemanse, Kerri A. Schoedel, M. Ufer

المصدر: European Neuropsychopharmacology. 40:S21-S22

مصطلحات موضوعية: Pharmacology, Zolpidem, Recreational Drug, business.industry, Suvorexant, Antagonist, Orexin receptor, Psychiatry and Mental health, Neurology, Medicine, Potential assessment, Pharmacology (medical), Neurology (clinical), business, Biological Psychiatry, medicine.drug

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::16090c1a26a54717f01336ed2e1c0c8eTest
https://doi.org/10.1016/j.euroneuro.2020.09.034Test

المؤلفون: Muehlan, C., Brooks, S., Zuiker, R., Gerven, J. van, Dingemanse, J.

المصدر: European Neuropsychopharmacology

مصطلحات موضوعية: Multiple-dose, Pharmacokinetics, Pharmacodynamics, Orexin receptor antagonist, Insomnia

الوصف: ACT-541468 is a dual orexin receptor antagonist with sleep-promoting effects in humans. Following entry-into-humans, its pharmacokinetics (PK) including dose-proportionality and accumulation, pharmacodynamics (PD), safety, and tolerability following multiple-ascending oral dose (MAD) administration in the morning, and next-day residual effects after repeated evening administration were investigated in a double-blind, placebo-controlled, randomized study. 31 healthy male and female subjects in 3 dose-groups (10, 25, and 75 mg) received study drug in the morning for 5 days (MAD part), and 20 healthy subjects received 25 mg in the evening for 1 week (evening part). PK, PD (saccadic peak velocity (SPV), adaptive tracking, body sway, Bond and Lader visual analogue scales (VAS), Karolinska Sleepiness Scale (KSS), VAS Bowdle for assessment of psychedelic effects), Digit Symbol Substitution Test (DSST), and Simple Reaction Time Test (SRTT), safety, and tolerability were assessed. ACT-541468 was absorbed with a median t(max) of 1.0-2.0 h across the 3 dose groups. The geometric mean elimination half-life (t(1/2)) on Day 5 was between 5.6 and 8.5 h, and the exposure (area under the curve (AUC)) showed dose proportionality. No accumulation and no influence of sex on the multiple-dose PK parameters of ACT-541468 was observed. No effects were observed at 10 mg. Administration of 25 and 75 mg during the day showed clear dose-dependent effects on the PD parameters, while next-day effects were absent after evening administration of 25 mg. The drug was safe and well tolerated. In conclusion, multiple-dose PK/PD of ACT-541468 were compatible with a drug designated to treat insomnia. (C) 2019 Elsevier B.V. and ECNP. All rights reserved. ; Stress-related psychiatric disorders across the life span

العلاقة: lumc-id: 81568884; https://hdl.handle.net/1887/122463Test

الإتاحة: https://doi.org/10.1016/j.euroneuro.2019.05.009Test
https://hdl.handle.net/1887/122463Test

المؤلفون: Arie Struyk, Cynthia Gargano, Junshui Ma, David Mayleben, S. Aubrey Stoch, Vladimir Svetnik, Melissa Drexel

المصدر: European Neuropsychopharmacology. 26:1649-1656

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Zolpidem, Pyridines, Polysomnography, Bedtime, Non-rapid eye movement sleep, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, mental disorders, medicine, Insomnia, Humans, Hypnotics and Sedatives, Pharmacology (medical), Biological Psychiatry, Aged, Pharmacology, Cross-Over Studies, medicine.diagnostic_test, business.industry, musculoskeletal, neural, and ocular physiology, Suvorexant, Electroencephalography, Azepines, Middle Aged, Triazoles, Sleep in non-human animals, Healthy Volunteers, Psychiatry and Mental health, 030104 developmental biology, Neurology, Anesthesia, Orexin Receptor Antagonists, Neurology (clinical), medicine.symptom, Sleep onset, Sleep, business, psychological phenomena and processes, 030217 neurology & neurosurgery, medicine.drug

الوصف: The objective of this study was to evaluate sleep electrophysiology in healthy subjects after bedtime administration of therapeutic doses of two insomnia treatments - the orexin receptor antagonist suvorexant or the GABAergic agonist zolpidem. Eighteen healthy men received single bedtime doses of suvorexant 20mg, zolpidem 10mg, or placebo in a double-blinded, randomized, balanced 3-period crossover study. EEG power spectral densities during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were recorded in a polysomnography (PSG) laboratory using a 19-lead EEG recording array. Spectral density was analyzed for each lead for frequencies between 1-32Hz. During NREM and REM sleep, zolpidem treatment reduced spectral density across theta and alpha frequency bands in all leads. In contrast, suvorexant had no significant effects on spectral density in any frequency band during NREM sleep, and modestly increased spectral density in the theta frequency band during REM sleep. Although the study was not designed to detect effects on PSG sleep endpoints in healthy subjects, both suvorexant and zolpidem increased mean total sleep time and sleep efficiency. Zolpidem reduced latency to persistent sleep whereas suvorexant did not. Suvorexant decreased wake after sleep onset, whereas zolpidem did not. These findings suggest that EEG power spectral density profile after administration of suvorexant in healthy subjects more closely approximates placebo sleep physiology than after zolpidem treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a4440483a80a1a3cf764b898298a5d6Test
https://doi.org/10.1016/j.euroneuro.2016.07.002Test

المؤلفون: N. Nachkebia, K. Bejanishvili, N. Maglakelidze, N. Rogava, E. Chkhartishvili, M. Babilodze, O. Mchedlidze

المصدر: European Neuropsychopharmacology. 40:S335

مصطلحات موضوعية: Pharmacology, Psychiatry and Mental health, Orexin-A, Neurology, Sleep wakefulness, business.industry, Muscarinic cholinergic, Medicine, Pharmacology (medical), Neurology (clinical), business, Neuroscience, Biological Psychiatry

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0b0852dc79836691e0652f0297c5432bTest
https://doi.org/10.1016/j.euroneuro.2020.09.432Test

المؤلفون: Pentti J. Tienari, Outi Vaarala, Emmanuel Mignot, Markku Partinen, Päivi Saavalainen, Hanna Ollila, Annika Wennerström, Markus Perola, Janna Saarela

المصدر: European Neuropsychopharmacology. 29:S994

مصطلحات موضوعية: Pharmacology, Whole genome sequencing, business.industry, medicine.disease, 3. Good health, 030227 psychiatry, Orexin, Genetic load, Vaccination, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Neurology, Pandemic, Immunology, medicine, Pharmacology (medical), Neurology (clinical), Genetic risk, business, 030217 neurology & neurosurgery, Biological Psychiatry, Exome sequencing, Narcolepsy

الوصف: Background Type 1 Narcolepsy is a severe hypersomnia caused by a specific loss of neurons producing hypocretin/orexin in the hypothalamus and affecting 1/3000 individuals. In 2009/2010 immunization towards pandemic H1N1 Influenza-A campaign was launched and the vaccine used in Northern European countries associated with increased risk for narcolepsy. Methods We built a multilocus genetic risk score with established narcolepsy risk variants using whole genome sequencing and exome sequencing data from 7,000 individuals to examine the genetic load for narcolepsy in 75 individuals with vaccination related narcolepsy, a third of all cases from Finland. Results Previously discovered risk variants had strong predictive power (P Discussion Our findings suggest that genetic risk factors have a major role in regulating predisposition for narcolepsy and genetic risk score gives high predictive power to detect individuals with high risk for narcolepsy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::7df7c822b1ebfd9621be04215e13c0bdTest
https://doi.org/10.1016/j.euroneuro.2017.08.379Test

المؤلفون: H. Raith, C. Dorner-Ciossek, P. Voehringer, J.R. Nicholson, B. Ferger

المصدر: European Neuropsychopharmacology. 27:S641-S642

مصطلحات موضوعية: Pharmacology, medicine.diagnostic_test, Chemistry, Blocking (radio), Electroencephalography, Orexin, Psychiatry and Mental health, Neurology, medicine, NMDA receptor, Pharmacology (medical), Neurology (clinical), Neuroscience, Biological Psychiatry

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::d063d06c07a246f39eb0279d49626073Test
https://doi.org/10.1016/s0924-977xTest(17)31205-1

المؤلفون: Petr D. Shabanov, E.A. Sekste, P.P. Khokhlov, E.R. Bychkov, M. I. Airapetov, A.A. Lebedev

المصدر: Publons

مصطلحات موضوعية: Pharmacology, medicine.medical_specialty, Ethanol, Orexin, Psychiatry and Mental health, chemistry.chemical_compound, Endocrinology, Neurology, chemistry, Internal medicine, medicine, Pharmacology (medical), Neurology (clinical), Receptor, Biological Psychiatry

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef8e8085d7536c951742f08535efa7ccTest
https://doi.org/10.1016/s0924-977xTest(17)31825-4