The Orexin/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress

Biomedicines, Год журнала: 2024, Номер 12(2), С. 448 - 448

Опубликована: Фев. 17, 2024

The orexin/hypocretin neuropeptide family has emerged as a focal point of neuroscientific research following the discovery that this plays crucial role in variety physiological and behavioral processes. These neuropeptides serve powerful neuromodulators, intricately shaping autonomic, endocrine, responses across species. Notably, they master regulators vigilance stress responses; however, their roles food intake, metabolism, thermoregulation appear complementary warrant further investigation. This narrative review provides journey through evolution our understanding orexin system, from its initial to promising progress made developing derivatives. It goes beyond conventional boundaries, striving synthesize multifaceted activities orexins. Special emphasis is placed on domains such response, fear, anxiety, learning, which authors have contributed literature with original publications. paper also overviews advancement pharmacology, already yielded some successes, particularly treatment sleep disorders.

Язык: Английский

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Drug development in psychiatry: 50 years of failure and how to resuscitate it

The Lancet Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Current models of insomnia disorder: a theoretical review on the potential role of the orexinergic pathway with implications for insomnia treatment

Journal of Sleep Research, Год журнала: 2023, Номер 32(4)

Опубликована: Фев. 14, 2023

Summary Insomnia disorder is considered as a stress‐related associated with hyperarousal, stress and emotion dysregulation the instability of ‘flip‐flop’ switch system. The orexinergic system well known for its key role in sleep arousal processes but also allostatic regulating emotions may thus be major interest insomnia treatment. Accordingly, we discuss potential orexins on processes, brain systems modulating implications pathophysiology. We reviewed available data effect dual orexin receptor antagonists (DORAs) stress/emotions present our findings narrative review. Few animals humans have reported that disrupted related to overactivation system, while some more consistent response acute disorders. Taken together these let us hypothesise an hyperarousal hyperactivation arousal‐promoting insomnia. On other hand, it possible by rebalancing DORAs regulate both systems, turn, contributing ‘switch off’ Nevertheless, studies are needed clarify evaluate effects sleep, systems.

Язык: Английский

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Clinical usefulness of dual orexin receptor antagonism beyond insomnia: Neurological and psychiatric comorbidities

Neuropharmacology, Год журнала: 2023, Номер 245, С. 109815 - 109815

Опубликована: Дек. 17, 2023

Orexin is a neurotransmitter produced by small group of hypothalamic neurons. Besides its well-known role in the regulation sleep-wake cycle, orexin system was shown to be relevant several physiological functions including cognition, mood and emotion modulation, energy homeostasis. Indeed, implication neurotransmission neurological psychiatric diseases has been hypothesized via direct effect exerted projections neurons brain areas, an indirect through orexin-mediated modulation sleep wake. Along with growing evidence concerning use dual receptor antagonists (DORAs) treatment insomnia, studies assessing their efficacy insomnia comorbid have set order investigate potential impact DORAs on both sleep-related symptoms disease-specific manifestations. This narrative review aimed at summarizing current conditions also discussing possible modulating for improving burden pathological mechanisms these disorders. Target searches were performed PubMed/MEDLINE Scopus databases ongoing registered Clinicaltrials.gov reviewed. Despite some contradictory findings, preclinical seemingly support beneficial antagonism management most common comorbidities. However, clinical research still limited further are needed corroborating promising preliminary results.

Язык: Английский

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Narcolepsy Severity Scale-2 and Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and consequences in Narcolepsy type 2

SLEEP, Год журнала: 2024, Номер 47(5)

Опубликована: Янв. 10, 2024

Narcolepsy type 2 (NT2) is an understudied central disorder of hypersomnolence sharing some similarities with narcolepsy 1 and idiopathic hypersomnia (IH). We aimed: (1) to assess systematically the symptoms in patients NT2, self-reported questionnaires: Epworth Sleepiness Scale (ESS), Severity (NSS), IH (IHSS), (2) evaluate responsiveness these scales treatment. One hundred nine NT2 (31.4 ± 12.2 years old, 47 untreated) diagnosed according ICSD-3 were selected a Reference Center for Narcolepsy. They all completed ESS, subgroups modified NSS (NSS-2, without cataplexy items) (n = 95) IHSS 76). Some twice (before/during treatment): 42 26 NSS-2, 30 IHSS. Based on untreated had sleepiness, 58% disrupted nocturnal sleep, 40% hallucinations, 28% sleep paralysis. On IHSS, 76% reported prolonged 83% inertia. In independent sample, ESS NSS-2 scores lower treated patients, same trend scores. After treatment, total lower, mean difference 3.7 4.1, 5.3 6.7, 4.1 6.2, respectively. The minimum clinically important between 2.1 3.3 3.1 61.9% decreased their > points, 61.5% 3 53.3% points. correctly quantified symptoms' severity consequences good performances objectify response medications. These tools are useful monitoring optimizing management, use clinical trials.

Язык: Английский

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From past to future: 50 years of pharmacological interventions to treat narcolepsy

Pharmacology Biochemistry and Behavior, Год журнала: 2024, Номер 241, С. 173804 - 173804

Опубликована: Июнь 7, 2024

The history of narcolepsy research began with the pioneering work Jean-Baptiste-Édouard Gélineau in late 19th century. In 1880s, introduced term "narcolepsy" to describe a condition characterized by sudden and uncontrollable episodes sleep. His clinical descriptions laid foundation for our understanding this complex disorder. Over last half-century, pharmacological landscape treatment has evolved remarkably, shifting from merely managing symptoms increasingly targeting its underlying pathophysiology. By 1930s, treatments such as ephedrine amphetamine were alleviate excessive daytime sleepiness, marking significant advancements management. These stimulants provided temporary relief, helping patients maintain wakefulness during day. As progressed, focus shifted towards disorder's mechanisms. discovery orexin (also known hypocretin) 1990s revolutionized field. This breakthrough underscored importance regulating sleep-wake cycles new targets intervention. Looking ahead, future pharmacotherapy is poised further innovation. ongoing exploration receptor agonists potential development neuroprotective therapeutic underscore promising horizon. Emerging into genetic immunological underpinnings opens avenues personalized medicine approaches identification biomarkers more precise strategies. Additionally, refinement existing through improved delivery systems investigation combination therapies offer opportunities enhanced efficacy quality life narcolepsy.

Язык: Английский

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Suvorexant alters dynamics of the sleep-electroencephalography-power spectrum and depressive-symptom trajectories during inpatient opioid withdrawal

SLEEP, Год журнала: 2024, Номер 47(4)

Опубликована: Янв. 30, 2024

Abstract Study Objectives Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine effects suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, their association with severity symptoms. Methods Participants use disorder (N = 38: age-range:21–63, 87% male, 45% white) underwent 11-day buprenorphine taper, in which they randomly assigned (20 mg [n 14] or 40 12]), placebo 12], while ambulatory sleep-EEG data was collected. Linear mixed-effect models used explore: (1) main interactive drug group, time power, (2) associations between change, symptoms, severity. Results Oscillatory spectral tended be greater groups. Over course study, decreases delta observed all groups (β −189.082, d −0.522, p <0.005), increases beta mg: β 2.579, 0.413, 0.009 | 5.265, 0.847, < 0.001) alpha 158.304, 0.397, 250.212, 0.601, sigma 48.97, 0.410, 0.001 71.54, 0.568, two During four-night associated 190.90, 0.308, 0.99 433.33, 0.889 <0.001), 215.55, 0.034, 0.006 192.64, −0.854, both −357.84, −0.659, 0.004 −906.35, −1.053, <0.001). Post-taper 740.58, 0.964 <0.001 662.23, 0.882, <0.001) only: 335.54, 0.560, 0.023) reduced group. Conclusions highlight a complex nuanced relationship depression withdrawal. Changes may represent mechanism influencing

Язык: Английский

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Seltorexant for major depressive disorder

Expert Opinion on Emerging Drugs, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Introduction Preclinical and clinical pharmacologic evidence indicate that orexin systems are relevant to sleep-wake cycle regulation dimensions of reward cognition, providing the basis hypothesizing they may be effective as therapeutics in mental disorders. Due limited efficacy tolerability profiles existing treatments for Major Depressive Disorder (MDD), investigational compounds novel treatment classes needed; seltorexant, an receptor antagonist, is a potential new currently under investigation.

Язык: Английский

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Comparison of efficacy and safety of dual orexin receptor antagonists lemborexant and daridorexant for the treatment of insomnia: a systematic review and meta-analysis

Psychopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Язык: Английский

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Effects mediated by melatonin and cortisol of artificial light and noise, alone and in combination, on sleep and health

Exploration of neuroscience, Год журнала: 2024, Номер 3(5), С. 382 - 417

Опубликована: Сен. 13, 2024

As an integral part of human chronobiology, the circadian system plays a crucial role in regulating key biological functions, including sleep and intricate hormonal rhythms melatonin (MLT) cortisol (CORT). Scholars have increasingly recognized environmental stressors as significant contributors to disturbed patterns. Albeit vigorously discussed individually, literature lacks comprehensive insights into synergistic effect artificial light at night (ALAN) noise. The aim this review is look interplay ALAN effects on architecture, modulation function, how influences homeostatic sleep. Furthermore, suppresses MLT secretion, which most pronounced response short wavelengths light. In addition, will demonstrate exposure noise during elevates CORT noradrenaline levels, contributes stress-related diseases disturbances. noise, persistently emitted environment, share intrinsic mechanisms with comparable characteristics. Therefore, understanding their combined impact has become urgent. Pre-sleep both acts potent stressor, potential disrupt Interestingly, sleep, emerges predominant influence quality. Moreover, these often synergize amplify one another’s adverse effects. Thus, limiting for cultivating sustainable environment conducive quality overall well-being.

Язык: Английский

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