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 $ α_{2} $-adrenergic receptor agonist, has become a popular sedative in intensive care, and hydroxyzine, a histamine receptor antagonist, is well known as a tranq...
Ausführliche Beschreibung

Purpose Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an $ α_{2} $-adrenergic receptor agonist, has become a popular sedative in intensive care, and hydroxyzine, a histamine receptor antagonist, is well known as a tranquilizing premedication for anesthesia. However, no experimental or pharmacological evaluation has been reported concerning their combination with propofol. Thus, we studied their combined effect with a hypnotic dose of propofol in ddY mice. Methods Male adult mice were intravenously administered either dexmedetomidine (30 μg/kg) or hydroxyzine (5 mg/kg) with propofol (3.75–10 mg/kg) to induce hypnosis, defined as a loss of the righting reflex (LRR). Other mice were intravenously administered propofol, dexmedetomidine (300 μg/kg), or hydroxyzine (50 mg/kg) alone, and subsequent behavioral changes were observed. The 50% effective dose ($ ED_{50} $) for LRR was calculated, and the duration of LRR was determined. Results The hypnotic dose of propofol was 9.95 ± 1.04 mg/kg ($ 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. 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. Ausführliche Beschreibung