title: Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: 2nd Department of Anesthesia, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kimura-Kuroiwa
authors.forename: Yushi U
authors.initials: YU
authors.lastname: Adachi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Obata
authors.forename: Mikito
authors.initials: M
authors.lastname: Kawamata
authors.forename: Shigehito
authors.initials: S
authors.lastname: Sato
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Matsuda
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D004357:Drug Synergism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006919:Hydroxyzine / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D006919:Hydroxyzine; D020927:Dexmedetomidine; D015742:Propofol