Department of Anesthesiology, ChanCheng Center Hospital, Foshan, China.
Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
J Chin Med Assoc. 2020 Feb;83(2):148-155. doi: 10.1097/JCMA.0000000000000236.
The aim of this study was to determine the effects of different concentrations of muscone on the ketamine requirement for hypnosis and analgesia and possible mechanism in mice.
In the hypnotic response experiment, muscone (0.5, 1.0, 2.0, 4.0, and 8.0 mg/kg) was administered 15 minutes before ketamine by intraperitoneal injection. The hypnotic response was evaluated by loss of righting reflex (LORR). In the analgesia experiment, muscone (0.5, 1.0, 2.0, and 4.0 mg/kg) was administered 15 minutes before 50 mg/kg ketamine injection. Pain threshold was assessed by measuring the tail-flick latency induced by heat radiation. Twenty minutes after ketamine injection, the mRNA expression of N-methyl-D-aspartate receptors (NR) subunits, γ-aminobutyric acid (GABA) receptors subunits, opioid receptors subunits, and some Na and Ca channels were detected by qPCR in the hippocampus of mice.
The 50% effective dose (ED50) with 95% confidence interval of ketamine-induced LORR was 49.2 (43.4-56.4) mg/kg. About 4.0 or 8.0 mg/kg muscone increased ED50 of ketamine-induced hypnosis, which was 82.7 (70.0-98.4) mg/kg or 72.0 (65.4-85.7) mg/kg, respectively. In the analgesic experiment, ketamine alone caused an obvious analgesic effect, whereas different dose of muscone decreased pain threshold in the presence of ketamine; 4.0 mg/kg muscone up-regulated the mRNA expression of NR1 and inhibited ketamine-induced increase of δ-opioid receptor mRNA level. Muscone also inhibited Cav2.1 mRNA expression in the presence of ketamine.
Muscone reduced the hypnotic and analgesic effect of ketamine in dose-independent manner in mice, which may be related to the changes of NR1 and δ-opioid receptor.
本研究旨在探讨不同浓度麝香酮对氯胺酮催眠和镇痛作用的影响及其可能的作用机制。
在催眠反应实验中，腹腔注射氯胺酮前 15 分钟给予不同浓度的麝香酮（0.5、1.0、2.0、4.0 和 8.0mg/kg），以翻正反射消失（LORR）评估催眠反应。在镇痛实验中，腹腔注射氯胺酮前 15 分钟给予不同浓度的麝香酮（0.5、1.0、2.0 和 4.0mg/kg），通过热辐射引起的尾巴摆动潜伏期来测量痛阈。20 分钟后，用 qPCR 检测各组小鼠海马中 N-甲基-D-天冬氨酸受体（NR）亚基、γ-氨基丁酸（GABA）受体亚基、阿片受体亚基和部分 Na 和 Ca 通道的 mRNA 表达。
氯胺酮诱导 LORR 的 50%有效剂量（ED50）为 49.2（43.4-56.4）mg/kg。4.0 或 8.0mg/kg 麝香酮可增加氯胺酮诱导催眠的 ED50，分别为 82.7（70.0-98.4）mg/kg 或 72.0（65.4-85.7）mg/kg。在镇痛实验中，单独使用氯胺酮可产生明显的镇痛作用，而不同剂量的麝香酮在存在氯胺酮的情况下降低痛阈；4.0mg/kg 麝香酮可上调 NR1 的 mRNA 表达，并抑制氯胺酮诱导的 δ-阿片受体 mRNA 水平的增加。麝香酮也抑制了 Cav2.1 mRNA 的表达。
麝香酮在小鼠体内以剂量非依赖性方式降低氯胺酮的催眠和镇痛作用，这可能与 NR1 和 δ-阿片受体的变化有关。
