Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice

Purpose

Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an ??₂-adrenergic receptor agonist, has become a popular sedative in intensive care, and hydroxyzine, a histamine receptor antagonist, is well known as a tranquilizing premedication for anesthesia. However, no experimental or pharmacological evaluation has been reported concerning their combination with propofol. Thus, we studied their combined effect with a hypnotic dose of propofol in ddY mice.

Methods

Male adult mice were intravenously administered either dexmedetomidine (30???g/kg) or hydroxyzine (5?mg/kg) with propofol (3.75?C10?mg/kg) to induce hypnosis, defined as a loss of the righting reflex (LRR). Other mice were intravenously administered propofol, dexmedetomidine (300???g/kg), or hydroxyzine (50?mg/kg) alone, and subsequent behavioral changes were observed. The 50% effective dose (ED₅₀) for LRR was calculated, and the duration of LRR was determined.

Results

The hypnotic dose of propofol was 9.95?±?1.04?mg/kg (ED₅₀?±?SEM) without combination. Dexmedetomidine and hydroxyzine reduced the ED₅₀ of propofol to 5.32?±?0.57 and 5.63?±?0.57?mg/kg, respectively. Coadministration of dexmedetomidine significantly extended LRR duration compared with propofol alone, whereas hydroxyzine significantly shortened LRR duration. A maximal dose of dexmedetomidine or hydroxyzine alone did not induce hypnosis.

Conclusions

Dexmedetomidine and hydroxyzine demonstrated no hypnotic action alone; however, their coadministration potentiated the hypnotic activity of propofol. Although reduction in the dose of propofol was similar, only dexmedetomidine prolonged the duration of hypnosis.