Lundy P M, Gowdey C W, Colhoun E H
Arch Int Pharmacodyn Ther. 1976 Apr;220(2):213-30.
The responses of rabbit aortic strips superfused with noradrenaline, adrenaline and 5-HT were studied alone and in combination with ketamine (50 mug/ml). Ketamine caused a slight depression of the isolated aorta but potentiated responses to adrenaline but not to noradrenaline or 5-hydroxytryptamine. Ketamine did not potentiate aortic strips contracted to a stable level by pyrogallol and adrenaline. Experiments carried out with COMT from homogenates of rat liver showed that, in contrast to pyrogallol (10(-5) M), ketamine (10(-3) M) did not inhibit the enzyme. Other experiments with rabbits given 6-hydroxydopamine showed that aortas of these rabbits responded in a similar manner to controls when treated with ketamine and catecholamines. Results obtained with aortas contracted by adrenaline and noradrenaline with ketamine present, followed by oil immersion, showed that ketamine prolonged greatly the relaxation induced by adrenaline and to a lesser extent the relaxation induced by noradrenaline. The results of these studies indicate that ketamine prevented catecholamines from reaching the intracellular site of COMT. In this respect, ketamine can be termed an inhibitor of uptake site 2. If this hypothesis is valid then the action of ketamine on vascular tissue might explain the cardiovascular effects of the drug in man and experimental animals.
研究了单独以及与氯胺酮（50微克/毫升）联合使用时，去甲肾上腺素、肾上腺素和5-羟色胺对兔主动脉条的作用。氯胺酮使离体主动脉略有抑制，但增强了对肾上腺素的反应，对去甲肾上腺素或5-羟色胺则无此作用。氯胺酮不能增强由焦性没食子酸和肾上腺素使主动脉条收缩至稳定水平的作用。用大鼠肝脏匀浆中的儿茶酚-O-甲基转移酶（COMT）进行的实验表明，与焦性没食子酸（10⁻⁵摩尔）不同，氯胺酮（10⁻³摩尔）不抑制该酶。用给予6-羟基多巴胺的兔子进行的其他实验表明，这些兔子的主动脉在用氯胺酮和儿茶酚胺处理时，反应与对照组相似。用肾上腺素和去甲肾上腺素使主动脉条收缩并加入氯胺酮，随后进行油浸，结果表明氯胺酮极大地延长了肾上腺素诱导的舒张，对去甲肾上腺素诱导的舒张延长程度较小。这些研究结果表明，氯胺酮阻止儿茶酚胺到达细胞内COMT位点。在这方面，氯胺酮可称为摄取位点2的抑制剂。如果这一假设成立，那么氯胺酮对血管组织的作用可能解释该药物在人和实验动物中的心血管效应。
