Leblanc P H, Buckner C K, Brunson D B, Laravuso R B, Will J A
Arch Int Pharmacodyn Ther. 1987 May;287(1):120-32.
Ketamine, 3 X 10(-4) M, was found to inhibit transmural electrical stimulation-induced contractile responses of the mainstem and hilar bronchi isolated from reserpine-pretreated guinea-pigs. This concentration of ketamine did not cause direct smooth muscle relaxation in these preparations and a smaller concentration (3 X 10(-5) M) was ineffective in blocking contractions. The pattern of inhibition produced by ketamine was similar to that produced by atropine, 1 X 10(-6) M, in both preparations and was observed at the larger stimulation frequencies employed. When studied in the presence of atropine to optimize noncholinergic-induced contractions, ketamine did not antagonize contractile responses to transmural electrical stimulation. After pretreatment of the isolated tissues with capsaicin, 1 X 10(-6) M, to optimize cholinergic-induced contractions, ketamine produced inhibition of responses to electrical stimulation. Ketamine, 3 X 10(-4) M, produced a shift to the right of the dose-response curve without altering the maximum contractile responses to carbachol, but had no effect on dose-response curves to substance P, the putative noncholinergic transmitter in these bronchial segments. The data suggest that ketamine exerts a selective inhibitory effect on cholinergically mediated contractions in guinea-pig bronchi and that this antagonism is largely exerted post-junctionally, at the level of the smooth muscle muscarinic receptors.
已发现，3×10⁻⁴M的氯胺酮可抑制从利血平预处理的豚鼠分离出的主支气管和肺门支气管的跨壁电刺激诱导的收缩反应。该浓度的氯胺酮在这些制剂中不会引起直接的平滑肌松弛，而较小浓度（3×10⁻⁵M）在阻断收缩方面无效。氯胺酮产生的抑制模式与1×10⁻⁶M阿托品在两种制剂中产生的抑制模式相似，并且在使用的较大刺激频率下也可观察到。当在阿托品存在下进行研究以优化非胆碱能诱导的收缩时，氯胺酮不会拮抗跨壁电刺激的收缩反应。在用1×10⁻⁶M辣椒素预处理分离的组织以优化胆碱能诱导的收缩后，氯胺酮对电刺激反应产生抑制作用。3×10⁻⁴M的氯胺酮使剂量 - 反应曲线向右移动，而不改变对卡巴胆碱的最大收缩反应，但对这些支气管节段中假定的非胆碱能递质P物质的剂量 - 反应曲线没有影响。数据表明，氯胺酮对豚鼠支气管中胆碱能介导的收缩具有选择性抑制作用，并且这种拮抗作用主要在节后平滑肌毒蕈碱受体水平发挥作用。
