Ann Sleep Med Res | Volume 4, Issue 1 | Research Article | Open Access
Haya Haj Yahya*, Amit Green, Soliman Khatib and Yaron Dagan
The Research Institute of Applied Chronobiology, Tel-Hai University, Upper Galilee, Israel
The Sleep and Fatigue Institute, Assuta Medical Center, Tel Aviv, Israel
Department of Biotechnology, Tel-Hai University, Upper Galilee, Israel
Natural Products and Analytical Chemistry Laboratory, MIGAL-Galilee Research Institute, Kyriat Shmona, Israel
*Correspondance to: Haya Haj Yahya
Fulltext PDFBenzodiazepines (BZs) interact with GABAA receptors, influencing neurotransmission and contributing to sedation and sleep regulation. Endogenous ligands for BZs, known as endozepines, have been implicated in sleep disorders, including recurrent stupor characterized by sudden sleep attacks. The current study investigates variations in endozepine levels, focusing on hypoxanthine as an endozepine, across diurnal and nocturnal periods in relation to daytime sleepiness. Eighteen subjects underwent overnight Polysomnography (PSG) followed by Multiple Sleep Latency Tests (MSLT). Blood samples collected at multiple time points were analyzed using LC-MS/MS for hypoxanthine concentrations. Subjects were categorized into "Sleepy" (mean sleep latency ≤ 9 minutes, consistent with community-based sleepiness thresholds) and "Not sleepy" groups based on MSLT results. The "sleepy" group exhibited significantly lower morning (06:00 h) hypoxanthine levels compared to the "not sleepy" group, but higher levels of hypoxanthine in the late morning (10:00 h) compared to the "not sleepy" group. Notably, the "sleepy" group displayed longer total sleep time during MSLT naps, higher sleep efficiency, a greater percentage of REM sleep, and a higher number of REM episodes in MSLT, suggesting a correlation between increased REM sleep and decreased hypoxanthine levels. These findings suggest a potential biomarker role for hypoxanthine in assessing daytime sleepiness and underscore the complex interplay between endozepines, REM sleep, and sleepiness disorders.
Endozepine; Hypoxanthine; REM; GABAA; Sleepiness; MSLT.
Haj Yahya H, Green A, Khatib S, Dagan Y. Exploring Hypoxanthine Endozepine as a Potential Biomarker for Daytime Sleepiness. Ann Sleep Med Res. 2026; 4(1): 1013..