Buccal Dexmedetomidine Promising Alternative for Enhanced Sleep Quality among people with insomnia, finds study

The locus coeruleus noradrenergic system could offer a promising avenue for treating insomnia with medication, especially in individuals experiencing heightened distress. Dexmedetomidine, a selective α2-noradrenergic agonist, reduces locus coeruleus activity at lower-than-anesthetic doses. However, there are currently no suitable non-injection methods available for administering dexmedetomidine. Recent study explores the buccal delivery of dexmedetomidine in addressing sleep disturbances. Two oromucosal formulations, sublingual and buccal, were tested for their pharmacokinetic and pharmacodynamic profiles in healthy individuals. Results showed that buccal dexmedetomidine was rapidly absorbed with minimal variability and dose proportionality. In poor sleepers, 40 µg buccal dexmedetomidine reduced sleep latency by 11.5 min, increased non-rapid eye movement (NREM) sleep time, and elevated NREM sleep electroencephalographic slow-wave energy. The onset of rapid eye movement (REM) sleep was dose-dependently delayed. Notably, cortisol, melatonin levels, heart rate, and postawakening parameters were not significantly affected.

Measurement and Pharmacokinetics

The study encompassed objective measurements like polysomnography, cortisol, melatonin assessments, and cardiovascular functions. The pharmacokinetics of both formulations were compared, showing superior performance of buccal delivery in terms of bioavailability and variability. The effects of 20 and 40 µg dexmedetomidine on sleep were studied in good and poor sleepers, revealing the rapid onset of action and enhanced NREM sleep in poor sleepers. The dexmedetomidine-induced changes did not affect cortisol levels, orthostatic regulation, or subjective sleep quality.

EEG Analysis and Implications

EEG analysis revealed increased slow-wave energy in NREM sleep with 40 µg dexmedetomidine, particularly in the first half of the night. The study showcased the potential of buccal dexmedetomidine in promoting NREM sleep in healthy poor sleepers, suggesting a role in enhancing sleep quality without adverse effects. The findings highlight buccal dexmedetomidine as a promising tool for investigating the locus coeruleus-norepinephrine system in sleep regulation and propose further clinical studies to validate its efficacy in treating stress-related insomnia. The study was supported by grants and declared potential conflicts of interest from some authors, with data availability upon request from the corresponding author.

Key Points

- Buccal delivery of dexmedetomidine demonstrated rapid absorption with minimal variability and dose proportionality, effectively reducing sleep latency by 11.5 min, increasing NREM sleep time, and enhancing NREM sleep electroencephalographic slow-wave energy in poor sleepers.

- Polysomnography, cortisol, melatonin assessments, and cardiovascular functions were used for objective measurements, revealing superior bioavailability and variability of buccal dexmedetomidine compared to sublingual delivery.

- The study showed that 20 and 40 µg dexmedetomidine induced rapid sleep onset and enhanced NREM sleep in poor sleepers without affecting cortisol levels, orthostatic regulation, or subjective sleep quality.

- EEG analysis demonstrated an increase in slow-wave energy during NREM sleep, especially in the first half of the night, highlighting the potential of buccal dexmedetomidine in promoting NREM sleep in healthy poor sleepers for improving sleep quality without adverse effects.

- The study suggested that buccal dexmedetomidine could be a valuable tool for investigating the locus coeruleus-norepinephrine system in sleep regulation and proposed further clinical studies to validate its efficacy in addressing stress-related insomnia.

- The research was funded by grants and disclosed potential conflicts of interest from some authors, with data accessibility available upon request from the corresponding author.

Reference –

MSc Laura K. Schnider et al. (2024). EFFECTS OF LOW-DOSE ORO-MUCOSAL DEXMEDETOMIDINE ON SLEEP AND THE SLEEP EEG IN HUMANS: A PHARMACOKINETICS-PHARMACODYNAMICS STUDY. Anesthesiology 2025; 142:476–88 https://doi.org/10.1101/2024.07.03.24309892