zaleplon / Generic mfg. - LARVOL DELTA

Zaleplon nanospanlastics loaded transdermal patches: formulation, optimization, ex-vivo permeation, and in-vivo studies. (PubMed, J Pharm Pharm Sci) - "The in-vivo studies have shown that the pharmacokinetic parameters of ZLP oral suspension and ZLP-SP1 are significantly different, with the relative bioavailability of ZLP-SP1 being 2.681%. Therefore, these fabricated transdermal patches could be effectively used to treat insomnia."

Journal • Preclinical • CNS Disorders • Insomnia • Sleep Disorder

Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis. (PubMed, Sleep Med) - "Comprehensively considering the efficacy effect size, time windows (follow-up period, age, and types of insomnia), PV, severity of imperative adverse events, we propose prioritizing the use of daridorexant 25 mg/d for insomnia characterized by difficulty maintaining sleep and insufficient sleep duration. For insomnia characterized by difficulty falling asleep, we recommend prioritizing the use of lemborexant 10 mg/day or zolpidem 10 mg/day. For overall poor sleep efficiency, we recommend using lemborexant. Drug selection should be based on the types of insomnia and drug safety. More head-to-head clinical trials are needed to confirm those findings."

Journal • Review • CNS Disorders • Insomnia • Pulmonary Disease • Sleep Disorder

Real-World Treatment Patterns of Sleep Medications in the United States Veterans Affairs Health System (WSS 2025) - "Overall, an estimated 2.6% were prescribed zolpidem, 0.7% temazepam, 0.28% eszopiclone, 0.12% ramelteon, 0.6% zaleplon, 0.5% suvorexant, 0.4% triazolam, 0.006 lemborexant, 0.005% estazolam, and 0.0001% daridorexant. The Z-drug zolpidem was the most commonly prescribed medication indicated for insomnia. Sedative antidepressants were also frequently utilized, likely due to their affordability and the lack of widely accepted, cost-effective alternatives for managing insomnia. This reliance on off-label agents such as trazodone suggests a potential gap between clinical guidelines and real-world practice, possibly reflecting formulary constraints, prescriber familiarity, or patient comorbidities."

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • Insomnia • Sleep Disorder

Effect of zaleplon on Cognitive Function of Insomnia Patients: a randomized, controlled multi-centre study (ChiCTR) - P=N/A | N=250 | Not yet recruiting | Sponsor: Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences); Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences

New trial • CNS Disorders • Insomnia • Sleep Disorder

Divergent synthesis of 3-formylpyrazolo[1,5-a]pyrimidines and methylene-bridged bis(pyrazolo[1,5-a]pyrimidines) using DMSO as a single carbon synthon. (PubMed, Org Biomol Chem) - "The reaction progressed through a radical pathway. The usefulness of 3-formylpyrazolo[1,5-a]pyrimidines in synthesizing a zaleplon derivative has been demonstrated."

Journal

Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis. (PubMed, Front Psychiatry) - "Compared with placebo, zolpidem (somnolence: relative risk [RR] 1.85; dizziness: RR 2.33; headache: RR 1.26), zopiclone (somnolence: RR 2.02; dizziness: RR 2.33; dysgeusia: RR 7.84), indiplon (somnolence: RR 3.46; dizziness: RR 2.30; headache: RR 1.63), gaboxadol (dizziness: RR 3.44), eszopiclone (somnolence: RR 2.00; dizziness: RR 3.18; dysgeusia: RR 10.54), estazolam (somnolence: RR 2.08), flunitrazepam (somnolence: RR 3.04), flurazepam (somnolence: RR 2.52), lemborexant (somnolence: RR 6.57), nitrazepam (somnolence: RR 3.80), Ramelteon (somnolence: RR 2.19), suvorexant (somnolence: RR 3.32), Temazepam (somnolence: RR 3.77), trazodone (somnolence: RR 2.86), triazolam (somnolence: RR 2.35), and esmirtazapine (somnolence: RR 4.63; dizziness: RR 2.87) had the most harmful profile in nervous system disorders...Data on some drugs like flurazepam, nitrazepam, triazolam, and zaleplon in some outcomes were mainly based on limited study with rare event and thus was highly..."

Adverse events • Journal • Retrospective data • Review • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Insomnia • Otorhinolaryngology • Pain • Psychiatry • Respiratory Diseases • Sinusitis • Sleep Disorder • Xerostomia

Physiologically based pharmacokinetic modeling of aldehyde oxidase drug-drug interactions mediated by erlotinib. (PubMed, Drug Metab Dispos) - "Recently, we characterized the epidermal growth factor receptor inhibitor erlotinib as a clinical AO inhibitor and proposed, through mechanistic metabolism studies and static modeling, that AO inhibition was responsible for its observed DDI with the investigational drug OSI-930...Additional simulations were also conducted to investigate untested clinical DDI scenarios between erlotinib and other known AO substrates-O6-benzylguanine, zaleplon, ziprasidone, and zoniporide...Additionally, our erlotinib model also predicts clinically significant DDIs would occur when dosing erlotinib with high fm,AO AO substrates. These findings highlight the need to consider AO inhibition in DDI risk assessments and may help inform future drug development and regulatory strategies."

Journal • PK/PD data • EGFR • SLCO2B1

Impact of cytosolic aldehyde oxidase contamination in liver microsomes on intrinsic clearance estimations. (PubMed, Drug Metab Dispos) - "Our results suggest that cytosolic AO contamination primarily impacts substrate depletion intrinsic clearance estimates for substrates with high AO clearance, but not those with moderate or low AO clearance, due to the apparent lack of turnover of O6-benzylguanine and zaleplon across all 3 batches of liver microsomes. SIGNIFICANCE STATEMENT: Our study underscores interindividual variability in hepatic aldehyde oxidase (AO) activity as the key determinant underlying residual AO activity in liver microsomes and illuminated the potential impact of cytosolic AO contamination on the reliability of intrinsic clearance estimates-emphasizing the need for substrate-specific strategies and refined in vitro methodologies in drug metabolism studies."

Journal

Sex Differences in Adverse Events Reported With Concomitant Buprenorphine and Insomnia Medications Use (CPDD 2025) - "Secondary search terms included commonly prescribed medications for insomnia: “temazepam”, “triazolam”, “estazolam”, “lorazepam”, “clonazepam”, “alprazolam”, “ramelteon”, “doxepin”, “trazodone”, “mirtazapine”, “suvorexant”, “lemborexant”, “daridorexant”, “quetiapine”, “hydroxyzine”, “gabapentin”, “eszopiclone”, “zaleplon”, “zolpidem”, “zolpidem ER”. Contrary to previous research demonstrating that females are involved in more AE reports across pharmacovigilance databases (Brabete et al., 2022), and that females taking 1 buprenorphine had an increased likelihood of insomnia medications prescription receipt, compared to their male counterparts (Martin et al., 2023), we did not find sex differences in the number of AE reports. However, the data suggest that males taking concomitant buprenorphine and insomnia medications, specifically benzodiazepines and DORAs, may experience more serious AEs than females."

Adverse events • CNS Disorders • Insomnia • Sleep Disorder

Treatment Patterns for Sleep Disorders in the United States Veterans Affairs Healthcare System (ISPOR 2025) - "Other treatments may include the melatonin receptor agonist (ramelteon) or sedating antidepressants (trazodone, off label)...Overall, an estimated 2.6% were prescribed zolpidem, 0.7% temazepam, 0.28% eszopiclone, 0.12% ramelteon, 0.06% zaleplon, 0.05% suvorexant, 0.04% triazolam, 0.006% lemborexant, 0.005% estazolam, and 0.001% daridorexant... The Z-drug zolpidem was the most commonly prescribed medication indicated for insomnia. Sedative antidepressants were also frequently utilized, likely due to their affordability and the lack of widely accepted, cost-effective alternatives for managing insomnia. Lemborexant and daridorexant, more recently approved for insomnia, were prescribed less frequently and have not yet become mainstream frontline treatments."

CNS Disorders • Insomnia • Sleep Disorder

Advances in Z-drug detection. (PubMed, Clin Chim Acta) - "The use of Z-drugs (zolpidem, zaleplon, zopiclone, and eszopiclone) has increased in recent years, leading to a growing need for analytical methods to accurately and reliably detect these compounds in biological samples. Recent studies have shown that these methods are effective in routine toxicological analysis and forensic detection of drug abuse. This review aims to provide a valuable resource for researchers and practitioners involved in the detection and analysis of Z-drugs, contributing to a better understanding and management of both therapeutic and illicit use of these compounds."

Journal • Review

A multicenter, open-label, randomized controlled study of the efficacy and safety of zaleplon in combination with escitalopram in the treatment of mild to moderate depression with insomnia (ChiCTR) - P4 | N=202 | Not yet recruiting | Sponsor: First Hospital of Shanxi Medical University; First Hospital of Shanxi Medical University

New P4 trial • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Improved clearance predictions for aldehyde oxidase substrates using a novel triculture human hepatocyte model. (PubMed, Drug Metab Dispos) - "CLh predictions generated using TruVivo for the reference compounds carbazeran, zoniporide, zaleplon, and O6-benzylguanine were within 2-fold of reported in vivo CL values...SIGNIFICANCE STATEMENT: The TruVivo in vitro primary human hepatocyte model maintains high levels of aldehyde oxidase (AO) activity for at least 14 days in culture, making the system suitable for evaluating slowly metabolized compounds, particularly those metabolized by AO. This novel system may therefore be useful for improving human clearance predictions for AO substrates."

Journal

Impact of Postoperative Sleep Medication Use on 90-Day Complications Following Total Knee Arthroplasty (AAOS 2025) - "We further analyzed the effects of standard prescription sleep medications (Daridorexant, Eszopiclone, Lemborexant, Suvorexant, Temazepam, Triazolam, Zaleplon, Zolpidem) and less potent prescription sleep medications (Doxepin, Ramelteon). Both standard and less potent prescription sleep medication use is associated with surgical complications. Post-operative sleep disturbance remains a major problem following TKA, but prescription sleep medications may be unsafe for routine postoperative use."

Insomnia • Musculoskeletal Diseases • Orthopedics • Pain • Sleep Disorder

Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group. (PubMed, Sleep Med) - "Discontinuation of Hypnotic Benzodiazepines and Z-drugs should be gradual, with dose reductions of 10-25 % each week. Multi-component CBT-I, daridorexant, eszopiclone, and melatonin 2 mg PR were shown to facilitate the gradual discontinuation of hypnotic benzodiazepines/Z-drugs within a cross-tapered program, which can be delayed when necessary. Finally, daridorexant and melatonin 2 mg PR do not require special switching or deprescribing protocols. Several sedative-hypnotic dosage reduction algorithms are proposed in this work for clinical use in real world settings."

Clinical guideline • Journal • Review • CNS Disorders • Insomnia • Sleep Disorder

Clinical applications of small-molecule GABAAR modulators for neurological disorders. (PubMed, Bioorg Chem) - "Benzodiazepines, such as Diazepam, are well-known positive allosteric modulators (PAMs) that enhance GABAAR function, providing therapeutic effects but also associated with side effects like sedation and dependence. Non-benzodiazepine modulators, including Z-drugs like Zolpidem and Zaleplon, offer improved selectivity for the α1 subunit of GABAAR, reducing some of these side effects. Neurosteroids such as allopregnanolone and its synthetic analogs, including Brexanolone, have emerged as potent GABAAR modulators with applications in conditions like postpartum depression and refractory epilepsy...Additionally, combining GABAAR modulators with other therapeutic agents has shown promise in enhancing efficacy and minimizing side effects. This review highlights the design strategies, pharmacodynamics, clinical efficacy, and safety profiles of these compounds, emphasizing the opportunities for developing novel GABAAR modulators with improved therapeutic outcomes."

Journal • Review • Anesthesia • CNS Disorders • Depression • Epilepsy • Insomnia • Mental Retardation • Mood Disorders • Postpartum Depression • Psychiatry • Sleep Disorder

Establishing a physiologically based pharmacokinetic framework for aldehyde oxidase and dual aldehyde oxidase-CYP substrates. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "PBPK models were developed for capmatinib, idelalisib, lenvatinib, zaleplon, ziprasidone, and zoniporide, incorporating in vitro functional data from human liver subcellular fractions and human hepatocytes. Subsequently, independent DDI studies with ketoconazole, itraconazole, rifampicin, and carbamazepine verified the fmCYP3A4, with predicted ratios of the area under the concentration-time curve (AUCR) within 1.5-fold of the observations. In conclusion, this study provides a novel PBPK-based framework for predicting AO-mediated pharmacokinetics and quantitative assessment of clinical DDI risks for dual AO-CYP substrates within a totality-of-evidence approach."

Journal • PK/PD data • CYP3A4

Study on effect of zaleplon capsules on subjective sleep quality and daytime function in patients with insomnia (ChiCTR) - P4 | N=360 | Not yet recruiting | Sponsor: ZhongDa Hospital, School of Medicine, Southeast University; ZhongDa Hospital, School of Medicine, Southeast University

New P4 trial • CNS Disorders • Insomnia • Sleep Disorder

Complete mitochondrial genome of Colias sifanica Grum-Grshimailo, 1891 (Lepidoptera: Pieridae) from montane region in northwestern China. (PubMed, Mitochondrial DNA B Resour) - "Phylogenetic analyses based on all PCGs using both the maximum likelihood and Bayesian inference methods indicated that C. sifanica is closely related to C. fieldii with high support values, and the phylogenetic relationship of (Dercas + ((Gandaca + Gonepteryx) + (Phoebis + (Anteos + (Catopsilia + (Zerene + Colias))))))) was shown for the tribe Coliadini. Though both the mitogenomic gene order and overall base composition were found to be conserved, different Ka/Ks ratios for several mitogenomic PCGs were detected between Colias and other species in the tribe Coliadini."

Journal

Trends in hypnotic drug use in depression 2007-2017: A Swedish population-based study. (PubMed, J Sleep Res) - "The most commonly used drugs were Z-drugs (zopiclone, zolpidem, and zaleplon) with a prevalence of 27.6% in 2017 and 35.6% in 2007 (PR 0.78, 95% CI 0.75-0.80)...Z-drugs use declined and melatonin use increased dramatically. Hypnotic drug use remained high even 3 years after diagnosis."

Journal • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Z-Drug Use and Benzodiazepine Use and Misuse Among LGB Populations: The Role of Psychological Distress. (PubMed, J Addict Med) - "The presence of psychological distress attenuates the disparities between LGB and heterosexual individuals in Z-drug use and BZD use and misuse."

Journal • CNS Disorders

Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. (PubMed, Brain Sci) - "This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon's mechanism of action."

Journal • Preclinical • CNS Disorders • Insomnia • Sleep Disorder

Behavioral Characterization of Zaleplon Effects in Rats: Further Evaluation and Influence on Glutamatergic Signalling in the Prefrontal Cortex (ACNP 2023) - "Our study demonstrated the memory-enhancing effects of repeatedly administrated zaleplon using an AA task in rats. To the best of our knowledge, our results are the first to show that low doses of zaleplon can support retrieval-based learning without sedative effects. Furthermore, the repeated administration of zaleplon may induce potential changes in glutamate-mediated neurotransmission."

Preclinical • CNS Disorders • SLC2A1

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers. (PubMed, Circulation) - "Our findings indicate that CD177 neutrophils may exert systemic pathological damage contributing to the shared morbidities in KD and MIS-C. We uncovered potential regulatory drivers of CD177 neutrophil hyperactivation and pathogenicity that may be targeted as a single therapeutic strategy for either KD or MIS-C."

Journal • Retrospective data • Cardiovascular • Celiac Disease • Dengue Fever • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Pediatrics • Rheumatoid Arthritis • Rheumatology • CD177 • S100A12 • SPI1

Predictive factors for severe outcomes in substance abuse-related emergency visits: A 5-year retrospective analysis at a medical center in Taiwan. (PubMed, J Chin Med Assoc) - "In Taiwan, benzodiazepines emerged as the most prevalent substance of abuse among emergency department visitors, and a significant proportion of these patients experienced severe outcomes. Continuous monitoring of severe outcome predictors is essential for enhanced understanding and management."

Biomarker • Journal • Retrospective data • Critical care • Endocrine Disorders • Infectious Disease • Pneumonia • Respiratory Diseases • Substance Abuse