A Case Study on Lemborexant and Zebrafish Sleep Models in Insomnia Research

Insomnia affects millions worldwide, often starts from an over expressive orexin system that keeps the brain in a prolonged wake up cycle. Lemborexant, a dual orexin receptor antagonist, reduces this hyper expression by blocking OX1R and OX2R receptors and promoting natural sleep with reduced sedation. Older therapies potentially caused drowsiness, narcolepsy episodes and some metabolic issues linked to CYP3A4.

Clinical sleep trials widely measured EEG and EMG to map brain activity, REM/non-REM transitions, locomotion and motor coordination. These assays demonstrated minimal impairment on following day and studies showed low withdrawal effects. These data helped to secure FDA approval based on improved sleep onset and maintenance.

Zebrafish models have rapidly emerged as a powerful vertebrate system of receptor antagonist in Insomnia research. Their conserved orexin signaling network and high scalability allow real-time behavioral and neuronal analysis.

Visualization of REM and NREM sleep transitions in Zebrafish Alzheimer's disease model, highlighting green circled areas of significant change.

Key zebrafish assays include 24-hr locomotor sleep tracking, which quantifies sleep bouts and latency. Light–dark transition tests that measure circadian disruption and arousal-threshold assays using vibrational stimuli to assess sleep depth. REM and non-REM sleep transitions (K Complex) to assess brain activity. Developmental toxicity, locomotion, motor coordination and CNS-interaction assays further evaluate safety.