Anesthetic properties of 4-iodopropofol: implications for mechanisms of anesthesia.
Anesthetic properties of 4-iodopropofol: implications for mechanisms of anesthesia.
复制标题
4-碘丙泊酚的麻醉特性：对麻醉机制的影响。
DOI：
10.1097/00000542-200106000-00020
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发表时间：
2001
期刊：
影响因子：
8.8
通讯作者：
HemmingsJr,HC
中科院分区：
文献类型：
--
作者：
Lingamaneni,R;Krasowski,MD;Jenkins,A;Truong,T;Giunta,AL;Blackbeer,J;MacIver,MB;Harrison,NL;HemmingsJr,HC
方法：观察异丙酚和4-碘异丙酚对重组人GABAA 1 2 2受体异源表达、大鼠海马片群体峰振幅和大鼠脑皮质突触体谷氨酸释放的影响。通过对非洲爪蟾蝌蚪、小鼠和大鼠进行腹腔注射和静脉注射后的翻正反射丧失来测定麻醉效力。结果：与异丙酚一样，4-碘异丙酚增强gaba诱导的重组GABAA受体电流，抑制大鼠海马片突触传递，抑制突触体中钠通道介导的谷氨酸释放，但作用减弱。腹腔注射后，4-碘异丙酚对小鼠不产生麻醉作用，但在血清和脑中未检测到。然而，4-碘异丙酚在蝌蚪（EC50 2.5 0.5 M）和大鼠静脉注射后（ED50 49 6.2 mg/kg）确实产生麻醉。结论：异丙酚和4-碘异丙酚对几个先前确定的全身麻醉作用的细胞和分子靶点产生相似的作用，两种化合物都能诱导蝌蚪和大鼠麻醉。4-碘异丙酚在啮齿类动物腹腔注射后不能诱导麻醉是由于异丙酚的药代动力学差异，而不是主要的药效学差异。
Methods: The effects of propofol and 4-iodopropofol were analyzed on heterologously expressed recombinant human GABAA 1 2 2 receptors, evoked population spike amplitudes in rat hippocampal slices, and glutamate release from rat cerebrocortical synaptosomes in vitro. Anesthetic potency was determined by loss of righting reflex in Xenopus laevis tadpoles, in mice after intraperitoneal injection, and in rats after intravenous injection.Results: Like propofol, 4-iodopropofol enhanced GABA-in-duced currents in recombinant GABAA receptors, inhibited synaptic transmission in rat hippocampal slices, and inhibited sodium channel–mediated glutamate release from synaptosomes, but with reduced potency. After intraperitoneal injection, 4-iodopropofol did not produce anesthesia in mice, but it was not detected in serum or brain. However, 4-iodopropofol did produce anesthesia in tadpoles (EC50 2.5 0.5 M) and in rats after intravenous injection (ED50 49 6.2 mg/kg).Conclusions: Propofol and 4-iodopropofol produced similar actions on several previously identified cellular and molecular targets of general anesthetic action, and both compounds induced anesthesia in tadpoles and rats. The failure of 4-iodopropofol to induce anesthesia in rodents after intraperitoneal injection is attributed to a pharmacokinetic difference from propofol rather than to major pharmacodynamic differences.