The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors

British Journal of Pharmacology, Год журнала: 2023, Номер 180(S2)

Опубликована: Окт. 1, 2023

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties approximately 1800 drug targets, and about 6000 interactions with 3900 ligands. There an emphasis on selective pharmacology (where available), plus links open access knowledgebase source targets their ligands ( https://www.guidetopharmacology.org ), which more detailed views target ligand properties. Although constitutes almost 500 pages, material presented substantially reduced compared information website. It a permanent, citable, point‐in‐time record that will survive database updates. full contents section can be found at http://onlinelibrary.wiley.com/doi/bph.16177 . G protein‐coupled receptors are one six major pharmacological into divided, others being: ion channels, nuclear hormone receptors, catalytic enzymes transporters. These nomenclature guidance summary best available tools, alongside references suggestions for further reading. landscape format designed facilitate comparison related from contemporary mid‐2023, supersedes data 2021/22, 2019/20, 2017/18, 2015/16 2013/14 Guides previous Receptors Channels. produced close conjunction Nomenclature Standards Committee International Union Basic Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification human where appropriate.

Язык: Английский

---

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

---

The orexin story, sleep and sleep disturbances

Journal of Sleep Research, Год журнала: 2022, Номер 31(4)

Опубликована: Июнь 13, 2022

Summary The orexins, also known as hypocretins, are two neuropeptides (orexin A and B or hypocretin 1 2) produced by a few thousand neurons located in the lateral hypothalamus that were independently discovered research groups 1998. Those peptides bind receptors (orexin/hypocretin receptor widely distributed brain involved central physiological regulation of sleep wakefulness, orexin 2 having major role maintenance arousal. They implicated multiplicity other functions, such reward seeking, energy balance, autonomic emotional behaviours. destruction is responsible for disorder narcolepsy with cataplexy (type 1) humans, defect signalling causes narcoleptic phenotype several animal species. Orexin discovery unprecedented history research, pharmacological manipulations may have multiple therapeutic applications. Several antagonists recently developed new drugs insomnia, agonists be next‐generation narcolepsy. Given broad range functions system, these might beneficial treating various conditions than disorders near future.

Язык: Английский

---

Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder

Neuropharmacology, Год журнала: 2023, Номер 226, С. 109418 - 109418

Опубликована: Янв. 6, 2023

Psychiatric disorders associated with psychological trauma, stress and anxiety are a highly prevalent increasing cause of morbidity worldwide. Current therapeutic approaches, including medication, effective in alleviating symptoms posttraumatic disorder (PTSD), at least some individuals, but have unwanted side-effects do not resolve underlying pathophysiology. After period stagnation, there is renewed enthusiasm from public, academic commercial parties designing developing drug treatments for these disorders. Here, we aim to provide snapshot the current state this field that written neuropharmacologists, also practicing clinicians interested lay-reader. introducing currently available treatments, summarize recent/ongoing clinical assessment novel medicines PTSD, grouped according primary neurochemical targets their potential produce acute and/or enduring effects. The evaluation putative targeting monoamine (including psychedelics), GABA, glutamate, cannabinoid, cholinergic neuropeptide systems, amongst others, discussed. We emphasize importance clinically assessing new medications based on firm understanding neurobiology stemming rapid advances being made neuroscience. This includes harnessing neuroplasticity bring about lasting beneficial changes brain rather than – as many transient attenuation symptoms, exemplified by combining psychotropic/cognitive enhancing drugs psychotherapeutic approaches. conclude noting other emerging trends promising phase development.

Язык: Английский

---

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

---

Sleep and vigilance states: Embracing spatiotemporal dynamics

Neuron, Год журнала: 2023, Номер 111(13), С. 1998 - 2011

Опубликована: Май 5, 2023

Язык: Английский

---

Targeting the orexin/hypocretin system for the treatment of neuropsychiatric and neurodegenerative diseases: From animal to clinical studies

Frontiers in Neuroendocrinology, Год журнала: 2023, Номер 69, С. 101066 - 101066

Опубликована: Апрель 1, 2023

Orexins (also known as hypocretins) are neuropeptides located exclusively in hypothalamic neurons that have extensive projections throughout the central nervous system and bind two different G protein-coupled receptors (OX1R OX2R). Since its discovery 1998, orexin has gained interest of scientific community a potential therapeutic target for treatment pathological conditions. Considering previous basic science research, dual receptor antagonist, suvorexant, was first agent to be approved by US Food Drug Administration treat insomnia. In this review, we discuss update main preclinical human studies involving with several psychiatric neurodegenerative diseases. This constitutes nice example how research driven curiosity can best route generation new powerful pharmacological treatments.

Язык: Английский

---

Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease

Heliyon, Год журнала: 2024, Номер 10(7), С. e28819 - e28819

Опубликована: Апрель 1, 2024

Sleep deprivation refers to an intentional or unintentional reduction in sleep time, resulting insufficient sleep. It is often caused by disorders, work demands (e.g., night shifts), and study pressure. promotes Aβ deposition tau hyperphosphorylation, which a risk factor for the pathogenesis progression of Alzheimer's disease (AD). Recent research has demonstrated potential involvement both AD through glial cell activation, lymphatic system, orexin circadian rhythm inflammation, gut microbiota. Thus, investigating molecular mechanisms underlying association between crucial, may contribute development preventive therapeutic strategies AD. This review aims analyze impact on AD, exploring pathological that link initiation offers theoretical foundation drugs aimed at preventing treating

Язык: Английский

---

Emerging and upcoming therapies in insomnia

Translational and Clinical Pharmacology, Год журнала: 2024, Номер 32(1), С. 1 - 1

Опубликована: Янв. 1, 2024

Insomnia, commonly treated with benzodiazepine (BZD) receptor agonists, presents challenges due to associated serious side effects such as abuse and dependence. To address these concerns, many researches have been conducted develop advance both pharmacological non-pharmacological interventions. Dual orexin antagonists (DORAs), which include suvorexant, daridorexant lemborexant, recently approved by United States Food Drug Administration (US FDA) a novel pharmacotherapeutic alternative. Unlike BZD agonists that act positive allosteric modulators of the gamma-aminobutyric acid type A subunit alpha 1 receptor, DORAs function binding types 2, inhibiting action wake-promoting neuropeptide. These drugs induce normal sleep without stage change, do not impair attention memory performance, facilitate easier awakening. However, more real-world safety information is needed. Selective orexin-2 (2-SORAs) under clinical developments. This review provides an overview mechanism in relation insomnia, pharmacokinetics, efficacy SORA. According insomnia management guidelines, first-line treatment for chronic cognitive behavioral therapy (CBT-I). Although it has proven effective improving sleep-related quality life, several restrictions limitations face-to-face format. Recently, prescription digital Somryst

Язык: Английский

---

Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation

Seminars in Immunopathology, Год журнала: 2022, Номер 44(5), С. 611 - 623

Опубликована: Апрель 21, 2022

Abstract Narcolepsy is a rare chronic neurological disorder characterized by an irresistible excessive daytime sleepiness and cataplexy. The disease considered to be the result of selective disruption neuronal cells in lateral hypothalamus expressing neuropeptide hypocretin, which controls sleep-wake cycle. Diagnosis management narcolepsy represent still substantial medical challenge due large heterogeneity clinical manifestation as well lack understanding underlying pathophysiological mechanisms. However, significant advances have been made last years, thus opening new perspective field. This review describes current knowledge presentation pathology existing diagnostic criteria therapeutic intervention for management. Recent evidence on potential immune-mediated mechanisms that may underpin establishment progression are also highlighted.

Язык: Английский

---