Daridorexant for the Treatment of Insomnia

Thomas²,

et al. 2023

Front. Nutr.

ObjectiveStress, sleep, and immunity are important interdependent factors that play critical roles in the maintenance of health. It has been established that stress can affect sleep, and the quality and duration of sleep significantly impact immunity. However, single drugs capable of targeting these factors are limited because of their multi-targeting mechanisms. The present study investigated the influence of a proprietary thymoquinone-rich black cumin oil extract (BCO-5) in modulating stress, sleep, and immunity.MethodsA randomized double-blinded placebo-controlled study was carried out on healthy volunteers with self-reported non-refreshing sleep issues (n = 72), followed by supplementation with BCO-5/placebo at 200 mg/day for 90 days. Validated questionnaires, PSQI and PSS, were employed for monitoring sleep and stress respectively, along with the measurement of cortisol and melatonin levels. Immunity markers were analyzed at the end of the study.ResultsIn the BCO-5 group, 70% of the participants reported satisfaction with their sleep pattern on day 7 and 79% on day 14. Additionally, both inter- and intra- group analyses of the total PSQI scores and component scores (sleep latency, duration, efficiency, quality, and daytime dysfunction) on days 45 and 90 showed the effectiveness of BCO-5 in the improvement of sleep (p < 0.05). PSS-14 analysis revealed a significant reduction in stress, upon both intra (p < 0.001) and inter-group (p < 0.001) comparisons. The observed reduction in stress among the BCO-5 group, with respect to the placebo, was significant with an effect size of 1.19 by the end of the study (p < 0.001). A significant correlation was also observed between improved sleep and reduced stress as evident from PSQI and PSS. Furthermore, there was a significant modulation in melatonin, cortisol, and orexin levels. Hematological/immunological parameters further revealed the immunomodulatory effects of BCO-5.ConclusionBCO-5 significantly modulated the stress-sleep-immunity axis with no side effects and restored restful sleep.

Section: Discussionmentioning

confidence: 99%

A proprietary black cumin oil extract (Nigella sativa) (BlaQmax®) modulates stress-sleep-immunity axis safely: Randomized double-blind placebo-controlled study

Thomas²,

et al. 2023

Front. Nutr.

Naunyn-Schmiedeberg's Arch Pharmacol

“…The endogenous ligands orexin A and orexin B are released in the hypothalamus and bind to orexin type 1 and type 2 receptors, which triggers wakefulness (Scammell and Winrow 2011 ). Antagonism of these receptors by daridorexant promotes sleep, reduces insomnia symptoms, and ameliorates sleep quality without causing addiction (Robinson et al 2022 ). The most frequent adverse events of daridorexant were nasopharyngitis, headache, fatigue, dizziness, nausea, and somnolence (Markham 2022 ).…”

Section: Neurologymentioning

confidence: 99%

“…The most frequent adverse events of daridorexant were nasopharyngitis, headache, fatigue, dizziness, nausea, and somnolence (Markham 2022 ). It has been emphasized that daridorexant should not be used concurrently with other central nervous system depressants as it may increase their effects (Robinson et al 2022 ).…”

Section: Neurologymentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2022

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2023

While new drug approvals by the U.S. Food and Drug Administration (FDA) had remained stable or even increased in the first 2 years of the COVID-19 pandemic, the 37 newly approved drugs in 2022 are considerably less than the 53 and 50 new drugs approved in 2020 and 2021, respectively, and less than the rolling 10-year average of 43. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition (“first-in-indication”), first drug using a novel molecular mechanism (“first-in-class”), and “next-in-class,” i.e., a drug using an already exploited molecular mechanism. We identify two “first-in-indication” (ganaxolon and teplizumab), 20 (54%) “first-in-class,” and 17 (46%) “next-in-class” drugs. By treatment area, rare diseases and cancer drugs were once again the most prevalent (partly overlapping) therapeutic areas. Other continuing trends were the use of accelerated regulatory approval pathways and the reliance on biopharmaceuticals (biologics).

“…The wakefulness-promoting effects of orexin have been validated in several multicenter, double-blind, randomized, placebo-controlled studies [115][116][117][118] and have recently been approved by the FDA for the treatment of adults who have insomnia. 119 Orexins are also associated with brain regions that regulate pain; 120 for example, orexins in the ventral tegmental area are associated with injurious responses. 121 Exogenously administered orexins have been shown to have analgesic effects in animal models.…”

Section: Orexinsmentioning

confidence: 99%

The Underlying Mechanisms of Sleep Deprivation Exacerbating Neuropathic Pain

Zhu¹,

Huang²

2023

NSS

Pain disrupts sleep, and sleep deprivation or interference can alter pain perception in animals and humans, for example by increasing sensitivity to pain. However, the mechanism by which sleep affects neuropathic pain remains unclear. In this review, we discuss the available evidence from the epidemiologic, clinical, and human, as well as laboratory studies. In previous studies, we have found that sleep deprivation affects various injurious systems, including opioids, dopaminergic, immune, orexins, hypothalamicpituitary-adrenal axis, and adenosine. At the same time, these systems play a crucial role in neuropathic pain regulation. In the complex interactions between these neurobiological systems, there may be potential regulatory pathways through which sleep deprivation amplifies neuropathic pain. Because of the impact sleep problems and neuropathic pain can have on the patients' quality of life, studying the link between sleep and neuropathic pain is important for neuropathic pain prevention and public health.