Sedative and Hypnotic Drugs
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Zaleplon, pyrazolopyrimidine derivative binds on the allosteric site as zolpidem on α1 receptor benzodiazepine subunit of the GABAA receptors. Presystemic metabolism reduces its oral bioavailability to about 30%. In 1 h, the drug reaches its peak plasma level after rapid absorption (Rosen et al., 1999). It is metabolized to inactive metabolites partly by hepatic aldehyde oxidase and cytochrome P450 isoform CYP3A4. In hepatic impairment patients and in geriatric age group, adjustment of dose may be required. It has interaction with drugs whose metabolism involves cytochrome P450 and aldehyde oxidase pathway (Rosen et al., 1999). Enzymes inhibitors may markedly increase the peak plasma concentration of zaleplon as they inhibit CYP3A4 and aldehyde dehydrogenase. Oxidation and glucuronidation of zaleplon produced soluble metabolites which are excreted through urine and reducing the plasma half-life to about 1 h. The drug is available in 5, 10, and 20 mg doses. Chronic or transient insomnia patient treated with zaleplon may experience shorter periods of sleep onset latency (Atkin et al., 2018).
Psychopharmacology EMIs
Michael Reilly, Bangaru Raju in Extended Matching Items for the MRCPsych Part 1, 2018
Buspirone.Chloral hydrate.Diazepam.Lorazepam.Paraldehyde.Sodium amytal.Temazepam.Zaleplon.Zolpidem.Zopiclone.
Medication effects on sleep
S.R. Pandi-Perumal, Meera Narasimhan, Milton Kramer in Sleep and Psychosomatic Medicine, 2017
The newer hypnotics zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta), and indiplon are agents that exert specific effects on the same GABA receptors (Figure 18.1). Benzodiazepine withdrawal is not blocked by these agents. These agents demonstrate excellent efficacy with minimal side effects. Although any agent used to induce sleep can result in a dependence on that agent for inducing sleep, the abuse potential of these agents is minimal. Idiosyncratic reactions of persistent daytime somnolence and/or memory loss have been reported in some patients. Tachyphylaxis is unusual, and these agents can be used on a long-term basis. Sleep is altered minimally, and REM rebound is not associated with these agents (Table 18.2).17,18 Zolpidem and eszopiclone have a 6–8-hour half-life, while zaleplon and indiplon are shorter acting (3–4 hours). Clinical comparison of these agents suggests that zolpidem and eszopiclone may have greater sleep-inducing efficacy, and zaleplon may have fewer side effects. Insomnia often occurs as a comorbid symptom in psychiatric and medical diagnoses associated nocturnal discomfort. While the importance of treating the underlying disorder cannot be overemphasized, these newer hypnotics can, in most cases, be safely utilized on a short-term basis for the treatment of such secondary/comorbid insomnia.
Rapid oral transmucosal delivery of zaleplon–lavender oil utilizing self-nanoemulsifying lyophilized tablets technology: development, optimization and pharmacokinetic evaluation
Published in Drug Delivery, 2022
Sarah A. Ali, Nabil A. Alhakamy, Khaled M. Hosny, Eman Alfayez, Deena M. Bukhary, Awaji Y. Safhi, Moutaz Y. Badr, Rayan Y. Mushtaq, Majed Alharbi, Bader Huwaimel, Mohammed Alissa, Sameer Alshehri, Ali H. Alamri, Taha Alqahtani
Zaleplon (ZP) is a fast-acting hypnotic drug of the pyrazolopyrimidine class with a mild adverse-effect profile. It is primarily recommended for the short-term management of insomnia (Ebbens & Verster, 2010; Manda et al., 2018). Insomnia may be described as frustration with sleep quality or quantity, trouble starting or maintaining sleep, and repeated nighttime awakenings. It affects 15% to 30% of the population at some point in their lives and is associated with depression, psychiatric illnesses, several other diseases and has significant socioeconomic consequences and is associated with a diminished quality of life (Buysse et al., 2008; Foda & Bakhaidar, 2010; Hosny & Banjar, 2013; Qaseem et al., 2016; Sakhare, 2017). Neither rebound insomnia nor dependence was observed on discontinuing zaleplon. However, sustained hypnotic efficacy was often achieved (Popescu, 2015; Dudhipala, 2016; Vermeeren et al., 2017).
GABAA receptor subtype modulators in medicinal chemistry: an updated patent review (2014-present)
Published in Expert Opinion on Therapeutic Patents, 2020
Letizia Crocetti, Gabriella Guerrini
An important category of α1-GABAA receptor modulators is represented by the so-called ‘Z-drugs’ (Figure 1), zaleplon, zolpidem, zopiclone, eszopiclone (S-enantiomer of zopiclone), marketed as Sonata®, Ambien®, Imovane®, and Lunesta®, respectively, that are structurally not related to classical benzodiazepines showing a pyrazolopyrimidine, imidazopyridine, and pyrrolopyrazine scaffold. Due to their preferential selectivity and efficacy at α1-containing GABAAR, they exhibit sedative properties, thus becoming the drugs of first choice in the treatment of insomnia from the 1990 s [31]. In the pharmacological treatment of insomnia is generally required to reduce sleep latency, increase sleep maintenance, improve sleep quality without affecting the next-day working state of patients. Pharmacokinetic studies and clinical trial outcomes indicate, for example, that zaleplon could be used for those patients with difficult to fall asleep but not for patients with sleep maintenance difficulties. Zolpidem improves sleep duration and the use of these drugs is convenient for its short duration of action and reduced sedation upon waking. Racemic zopiclone reduces sleep latency and increases total sleep time but its utility is limited since it impairs next-day functioning. In addition to preferential modulation at α1-containing GABAAR, racemic zoplicone also significant binds other GABAAR subtypes; thus, further pharmacological effects, it could be expected. Eszopiclone, the (S)-enantiomer of zopiclone does not affect the next-day functioning and alertness and does not show tolerance, dependence, or rebound insomnia under long-term treatment [32].
Zolpidem high-dose abuse: what about the liver? Results from a series of 107 patients
Published in Expert Opinion on Drug Safety, 2019
Fabio Lugoboni, Antonio Mirijello, Laura Morbioli, Marco Faccini, Rebecca Casari, Salvatore De Cosmo, Antonio Gasbarrini, Giovanni Addolorato
A total of 107 HD-ZLM abuse and 3 HD-zopiclone abuse patients met the eligibility criteria (Figure 1) and their medical records were reviewed. The three zopiclone-addicted patients were excluded from further evaluation given the lack of conversion tables to diazepam equivalents and because of the low number of this subgroup of patients. No zaleplon-addicted patients were treated in the evaluated period. Main characteristics of the sample are summarized in Tables 1 and 2.
Related Knowledge Centers
- Cyp3A4
- Insomnia
- NONbenzodiazepine
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- Benzodiazepine
- Sedative
- Hypnotic
- Pyrazolopyrimidine
- Rebound Effect
- Cyp3A4
- Liver Function Tests