Pharmacokinetics of nicotine in adult and infant mice.
Pharmacokinetics of nicotine in adult and infant mice.
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尼古丁在成年和幼年小鼠中的药代动力学。
DOI：
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发表时间：
1977
期刊：
影响因子：
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通讯作者：
M. Mattila
中科院分区：
文献类型：
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作者：
R. Mansner;M. Mattila
研究人员进行了实验，比较小剂量和大剂量单剂量放射性酒石酸尼古丁后，婴儿和成年小鼠的血液、心脏和大脑中尼古丁浓度的时间进程。在一些实验中，尼古丁受体被美加明或六甲铵阻断，并测量了它们对尼古丁水平的影响。允许目视尼古丁引起的震颤，并通过心电图测量其对心率的影响。成年小鼠脑内尼古丁水平在 10 分钟时达到峰值，而幼年小鼠脑内尼古丁水平在 20 分钟时仍在上升。后者的血液和心脏尼古丁水平高于各自的大脑水平，脑干中的尼古丁水平超过了半球水平。结果在成年小鼠身上出现了逆转。测量到婴儿心脏中尼古丁的显着积累。美加明预处理降低了成年小鼠大脑中的尼古丁水平，而幼年小鼠中血液和心脏中的尼古丁水平也降低了。这种预处理在两个年龄组中消除了尼古丁震颤及其对心率的影响。这表明，婴儿和成年小鼠在使用美加明后尼古丁水平的差异可能不仅仅取决于循环变化的可能差异，而且也可能代表“受体群体”的差异。六甲铵并没有消除尼古丁对心率的中枢抑制作用，也没有降低大脑中的尼古丁水平。这支持了尼古丁的中枢作用与其大脑水平之间存在某种相关性的观点。
Experiments were done to compare the time-courses of the nicotine concentration in the blood, heart, and brain of infant and adult mice after small and large single doses of radioactive nicotine tartrate. In some experiments the nicotine receptors were blocked with mecamylamine or hexamethonium, and their effects on nicotine levels were measured. The nicotine-induced tremor was allowed visually, and its effects on the heart rate were measured by ECG. In adult mice the peak levels of brain nicotine occurred at 10 min, whereas in infant mice the brain nicotine levels were still rising at 20 min. In the latter the blood and heart nicotine levels were higher than the respective brain levels, and the nicotine level in the brain stem exceeded the hemisphere level. The results were reversed in adult mice. A remarkable accumulation of nicotine in the infant heart was measured. Pretreatment with mecamylamine lowered brain nicotine levels in adult mice, and in infant mice the nicotine levels in blood and heart were lowered as well. This pretreatment abolished the nicotine tremor and its effects on the heart rate similarly in both age groups. This suggests that the difference in nicotine levels after mecamylamine in infant and adult mice may not depend solely on possible differences in circulatory changes but can represent differences in "receptor population" as well. Hexamethonium did not abolish the central depressant effect of nicotine on the heart rate nor did it lower the brain nicotine levels. This supports the view that there is some correlation of the central effects of nicotine and its brain levels.