Published in:
01-06-2012 | Original Article
Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice
Published in: Journal of Anesthesia | Issue 3/2012
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Purpose
Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an α2-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 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 (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.