China
Africa
Explore chapters and articles related to this topic
Sedative and Hypnotic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Arup Kumar Misra, Pramod Kumar Sharma
Zolpidem, eszopiclone, and zaleplon are collectively known as “Z-drugs” though they have the same mechanism of action as benzodiazepines but they are structurally unrelated (Gregory, 2016). Ramelteon and tasimelteon are the melatonin receptor agonists which are approved by US FDA as newer hypnotics indicated for non-24-h sleep–wake disorders (Laudon, 2014). An orexin receptor antagonist, suvorexant was introduced in the market in August 2014 and is indicated to improve sleep duration. Buspirone is a slow-onset anxiolytic agent differing from the conventional sedative–hypnotics in their mechanism of action (Mendelson, 1990).
The metabolism of the dual orexin receptor antagonist daridorexant
Published in Xenobiotica, 2023
Alexander Treiber, Stephane Delahaye, Aude Weigel, Päivi Aeänismaa, John Gatfield, Swen Seeland
A number of low molecular weight insomnia drugs have been discovered recently targeting either both orexin receptors, or selectively the OX2 receptor subtype. Their pharmacological mode of actions differs from those of classical sleep-promoting agents, which act rather as sedatives or hypnotics. The field was pioneered by the dual orexin receptor antagonist almorexant in 2007 (Brisbare-Roch et al. 2007), followed by suvorexant, lemborexant, and others (Cox et al. 2010; Coleman et al. 2012; Drahl 2014; Letavic et al. 2015; Yoshida et al. 2015). Suvorexant was the first orexin receptor antagonist receiving US regulatory approval in 2014, marketed under the tradename Belsomra®. Suvorexant reduces the time to sleep onset and time to wake after sleep onset in a dose-dependent manner. Due to its long half-life of 12 h, the positive effects on sleep parameters were accompanied by next-morning residual effects, eventually leading to the approval of suboptimal doses for sleep therapy (Citrome 2014; Herring et al. 2016). The dual antagonist daridorexant resulted from a tailored discovery program whose main focus was to balance an appropriate duration of action with the absence of next-morning residual effects, using physiology-based pharmacokinetic/pharmacodynamic (PBPK/PD) modelling (Treiber et al. 2017). Model predictions were confirmed in two recently completed phase 3 programs (Mignot et al. 2022). Daridorexant was approved by the US FDA in 2022 as well as in the EU in 2023.
Evaluating lemborexant for the treatment of insomnia
Published in Expert Opinion on Pharmacotherapy, 2021
DORAs are a newer class of medication for treating insomnia that target the orexin signaling pathway that promotes wakefulness through a complex signaling pathway in the brain (detailed information is provided in Janto et al. [43]). For insomnia, DORAs work by blocking binding of the two types of orexin molecules (orexin-A and -B) to the two types of orexin receptors (orexin receptor-1 and −2), thereby promoting sleep [43]. Suvorexant was the first DORA approved by the FDA for the treatment of insomnia with an indication of treating difficulties with sleep onset and/or sleep maintenance, and is recommended by the AASM clinical practice guidelines for the treatment of sleep maintenance insomnia [19,44]. The most common adverse event associated with suvorexant is daytime sedation, or somnolence, and suvorexant is associated with higher incidences of somnolence, abnormal dreams, fatigue, dry mouth, and rebound insomnia compared with placebo [45]. Although complex sleep behaviors and cataplexy have been reported with suvorexant, there was no difference versus placebo in a meta-analysis [45].
Selecting a pharmacotherapy regimen for patients with chronic insomnia
Published in Expert Opinion on Pharmacotherapy, 2020
Amanda B. Hassinger, Nikolas Bletnisky, Rizwan Dudekula, Ali A. El-Solh
A representative of a new class of hypnotics, the orexin receptor antagonists, suvorexant, has been approved by the FDA in August 2014 for the treatment of primary insomnia of the sleep-onset and sleep-maintenance subtypes. However, suvorexant increases nocturnal sleep mainly by reducing wake after sleep onset (WASO) [47,48]. Suvorexant effect on sleep onset is substantially weaker compared to other short-acting hypnotics like zaleplon or triazolam. Despite the limited safety data on its prolonged use, our approach still favors the use of this agent for coexisting sleep onset and sleep-maintenance insomnia because difficulty staying asleep is more common than difficulty falling asleep particularly for patients over the age of 40 [49]. The current recommended dose is 10 mg to 20 mg daily. Like most hypnotics, suvorexant can be responsible for daytime sleepiness, fatigue, narcolepsy-like symptoms, and in rare instances suicidal ideation [49]. Lemborexant is the most recent drug in the orexin receptor antagonists class to receive approval from the FDA for the treatment of sleep onset and or sleep-maintenance insomnia [50]. Its mechanism of action parallels that of suvorexant. Similar to non-benzodiazepine benzodiazepine-receptor agonists, both suvorexant and lemborexant are a schedule IV controlled substance.