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Journal of anesthesia

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


PMID 22349749

Abstract

Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an α(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. Male adult mice were intravenously administered either dexmedetomidine (30 μg/kg) or hydroxyzine (5 mg/kg) with propofol (3.75-10 mg/kg) to induce hypnosis, defined as a loss of the righting reflex (LRR). Other mice were intravenously administered propofol, dexmedetomidine (300 μg/kg), or hydroxyzine (50 mg/kg) alone, and subsequent behavioral changes were observed. The 50% effective dose (ED(50)) for LRR was calculated, and the duration of LRR was determined. The hypnotic dose of propofol was 9.95 ± 1.04 mg/kg (ED(50) ± SEM) without combination. Dexmedetomidine and hydroxyzine reduced the ED(50) 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. 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.

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