Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice
Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice
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DOI：
10.1007/s00540-012-1344-3
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发表时间：
2012-06-01
影响因子：
2.8
通讯作者：
Matsuda, Naoyuki
中科院分区：
文献类型：
--
作者：
Kimura-Kuroiwa, Kaori;Adachi, Yushi U.;Matsuda, Naoyuki
研究麻醉剂相互作用的特征可能为麻醉机制提供线索。右美托咪定是一种α（2）-肾上腺素能受体激动剂，已成为重症监护中常用的镇静剂，羟嗪是一种组胺受体拮抗剂，是众所周知的麻醉前镇静药。然而，没有关于其与丙泊酚组合的实验或药理学评价的报道。因此，我们在ddY小鼠中研究了它们与催眠剂量的丙泊酚的联合作用。雄性成年小鼠静脉内施用右美托咪定（30 μ g/kg）或羟嗪（5 mg/kg）与丙泊酚（3.75-10 mg/kg）以诱导催眠，定义为翻正反射（LRR）的丧失。其他小鼠单独静脉给予丙泊酚、右美托咪定（300 μ g/kg）或羟嗪（50 mg/kg），观察随后的行为变化。计算LRR的半数有效剂量（ED_（50）），并测定LRR持续时间，未联合用药时，丙泊酚的催眠剂量为9.95 ± A1.04mg/kg（ED_（50）± ASEM）。右美托咪定和羟嗪分别将丙泊酚的ED 50降低至5.32 +/- A 0.57和5.63 +/- A 0.57 mg/kg。与丙泊酚单独给药相比，右美托咪定联合给药显著延长LRR持续时间，而羟嗪显著缩短LRR持续时间。单独使用最大剂量的右美托咪定或羟嗪不能诱导催眠，单独使用右美托咪定和羟嗪没有催眠作用，但是，它们的联合给药增强了丙泊酚的催眠活性。虽然丙泊酚剂量的减少相似，但只有右美托咪定延长了催眠持续时间。
Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an alpha(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 mu g/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 mu 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.The hypnotic dose of propofol was 9.95 +/- A 1.04 mg/kg (ED50 +/- A SEM) without combination. Dexmedetomidine and hydroxyzine reduced the ED50 of propofol to 5.32 +/- A 0.57 and 5.63 +/- A 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.