2nd Department of Anesthesia, Nagano Red Cross Hospital, Nagano, Japan.
J Anesth. 2012 Jun;26(3):422-8. doi: 10.1007/s00540-012-1344-3. Epub 2012 Feb 18.
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.
研究麻醉药物相互作用的特点可能为揭示麻醉机制提供线索。右美托咪定是一种 α（2）-肾上腺素能受体激动剂，在重症监护病房中已成为一种常用的镇静剂，而羟嗪作为麻醉前的镇静剂，其作为组胺受体拮抗剂广为人知。然而，尚未有关于其与异丙酚联合使用的实验或药理学评价的报道。因此，我们研究了它们与异丙酚催眠剂量联合使用对 ddY 小鼠的影响。
雄性成年小鼠静脉注射右美托咪定（30μg/kg）或羟嗪（5mg/kg），并给予异丙酚（3.75-10mg/kg）以诱导催眠，定义为翻正反射（LRR）丧失。其他小鼠单独静脉注射异丙酚、右美托咪定（300μg/kg）或羟嗪（50mg/kg），并观察随后的行为变化。计算 LRR 的 50%有效剂量（ED（50）），并确定 LRR 的持续时间。
未联合用药时，异丙酚的催眠剂量为 9.95±1.04mg/kg（ED（50）±SEM）。右美托咪定和羟嗪将异丙酚的 ED（50）分别降低至 5.32±0.57mg/kg 和 5.63±0.57mg/kg。与单独使用异丙酚相比，右美托咪定联合用药显著延长了 LRR 持续时间，而羟嗪则显著缩短了 LRR 持续时间。单独使用最大剂量的右美托咪定或羟嗪均不能诱导催眠。
右美托咪定和羟嗪单独使用时没有催眠作用；然而，它们的联合使用增强了异丙酚的催眠活性。虽然减少的异丙酚剂量相似，但只有右美托咪定延长了催眠持续时间。
