Effects of Sub-Anesthetic Oro-Mucosal Dexmedetomidine on Sleep in Humans: A Randomized, Controlled Pharmacokinetics-Pharmacodynamics Study

The locus coeruleus (LC) noradrenergic system may provide a potential new target for pharmacological insomnia treatment, particularly in patients suffering from elevated distress. The selective α2 noradrenergic agonist dexmedetomidine attenuates LC activity in sub-anesthetic doses, yet no adequate non-parental delivery systems of dexmedetomidine are currently available. To examine the feasibility of oro-mucosal dexmedetomidine administration, we developed two distinct - one sublingual and one buccal - oro-mucosal, fast-disintegrating dexmedetomidine formulas tailored for self-administration. Here we established their pharmacokinetic and pharmacodynamic (PK-PD) profiles.