Dexmedetomidine Hydrochloride

Weerink MAS, et al. examined the clinical pharmacology of dexmedetomidine, a highly selective α₂-adrenoceptor agonist (α₂:α₁ ratio 1620:1) with sedative, anxiolytic, sympatholytic, and opioid-sparing properties. Its hypnotic effect occurs through activation of central α₂-receptors in the locus coeruleus, inducing unconsciousness that resembles natural sleep while maintaining patient arousability and cooperation. Although initially approved for short-term intensive care unit sedation, the applications of dexmedetomidine have expanded to include procedural sedation and various off-label uses, including pediatric sedation, alternative routes of administration, and adjunctive analgesia.

Fig. 1 Simulated concentration time profiles according to the different reported adult population pharmacokinetic models. (Weerink MAS, et al., 2017)

Mei B, et al. investigated the neuroprotective mechanisms of dexmedetomidine in a mouse model of sepsis-associated encephalopathy induced by cecal ligation and puncture. Dexmedetomidine treatment reduced systemic and hippocampal proinflammatory cytokine levels (TNF-α, IL-6, IL-1β), decreased blood-brain barrier permeability, and prevented cognitive deficits as assessed by the Barnes maze and fear conditioning tests. These protective effects were blocked by intracerebroventricular administration of α₂-adrenoceptor antagonists, specifically the α₂A-selective antagonist BRL-44408. Immunohistochemistry revealed that astrocytes, but not microglia, expressed α₂A adrenoceptors, and microglial depletion did not abolish the effects of dexmedetomidine.

Fig. 2 Dexmedetomidine attenuated sepsis-impaired learning, memory and BBB integrity in mice. (Mei B, et al, 2021)