OPIATE‐LIKE ANALGESIC ACTIVITY IN GENERAL ANAESTHETICS
OPIATE‐LIKE ANALGESIC ACTIVITY IN GENERAL ANAESTHETICS
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全身麻醉中的阿片类镇痛活性
DOI：
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发表时间：
1981
影响因子：
7.3
通讯作者：
A. Livingston
中科院分区：
文献类型：
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作者：
D. Lawrence;A. Livingston
1在体内和体外研究了纳洛酮与不同麻醉药的相互作用。2纳洛酮（10 mg/kg）对氟烷、乙醚、氯胺酮、戊巴比妥和Althesin的麻醉持续时间无明显影响。3在大鼠甩尾试验中，纳洛酮（10 mg/kg）可降低氧化亚氮、氯胺酮和吗啡的镇痛活性。除戊巴比妥和Althesin外，其他麻醉剂也诱导镇痛，但不被纳洛酮拮抗。4特异性[3 H]-二氢吗啡结合被阿片类药物纳洛酮（IC 50 = 7.6 nM）、甲硫氨酸-脑啡肽（Met-脑啡肽，IC 50 = 40 nM）和吗啡（IC 50 = 54 nM）取代。同样，甲苯噻嗪（IC 50 =9μ m）、氯胺酮（IC 50 = 130μm）和Althesin（IC 50 = 150 μm）也观察到置换;其他检测的麻醉剂在mM浓度下无活性。5氯胺酮（IC 50 =200 μm）和甲苯噻嗪（IC 50 =9.5 μ m）也能够取代特异性[3 H]-D-Ala 2-脑啡肽（D-Leu）结合，吗啡（IC 50 = 95 nM）和甲硫氨酸脑啡肽（IC 50 = 40 nM）也是如此。6在刺激的豚鼠回肠上，甲硫氨酸和吗啡抑制收缩，IC 50值分别为30 nM和50 nM。麻醉剂氯胺酮（IC_（50）= 10μm）和Althesin（IC_（50）= 8μ m）具有活性。赛拉嗪（IC 50 = 12 nM）在抑制该制剂的收缩方面表现出相当大的效力。纳洛酮0.5 μ M使阿片剂量反应曲线偏移1000倍，但麻醉反应对纳洛酮的拮抗作用仅显示轻微敏感性。7发现Althesin的活性是由于该麻醉剂溶解于其中的媒介物。8虽然几种麻醉剂显示出镇痛活性、特异性二氢吗啡结合置换或豚鼠回肠抑制活性，但这些作用对纳洛酮的敏感性不同。
1 The interaction of naloxone with various anaesthetics was studied both in vivo and in vitro. 2 Naloxone (10 mg/kg) did not significantly alter the anaesthetic duration of halothane, diethylether, ketamine, pentobarbitone or Althesin. 3 Naloxone (10 mg/kg) reduced the analgesic activity of nitrous oxide, ketamine and morphine in the rat tail‐flick test. With the exception of pentobarbitone and Althesin, the other anaesthetic agents also induced analgesia but were not antagonized by naloxone. 4 Specific [3H]‐dihydromorphine binding was displaced by the opiates naloxone (IC50=7.6nM), methionine‐enkephalin (Met‐enkephalin, IC50=40nM) and morphine (IC50=54nM). Similarly, displacement was observed with xylazine (IC50=9μ,m), ketamine (IC50 = 130μm) and Althesin (IC50 = 150 μm); other anaesthetics agents tested were inactive in mM concentrations. 5 Ketamine (IC50 =200 μm) and xylazine (IC50 =9.5 μ,m) were also capable of displacing specific [3H]‐D‐Ala2‐enkephalin (D‐Leu) binding, as were morphine (IC50 = 95 nM) and Met‐enkephalin (IC50 = 40nM). 6 On the stimulated guinea‐pig ileum, Met‐enkephalin and morphine inhibited the contractions, the IC50 values were 30 nM and 50 nM respectively. The anaesthetics ketamine (IC50 = 10μm) and Althesin (IC50 = 8μ,m) were active. Xylazine (IC50 = 12nM) exhibited considerable potency in inhibiting the contractions on this preparation. Naloxone 0.5 μ,M produced a 1000 fold shift in the opiate dose‐response curve but the anaesthetic responses showed only slight sensitivity to antagonism by naloxone. 7 The activity of Althesin was found to be due to the vehicle in which this anaesthetic is solubilised. 8 Whilst several anaesthetic agents showed analgesic activity, specific dihydromorphine binding displacement or guinea pig ileum inhibiting activity, these effects showed variable sensitivity to naloxone.