The pharmacology of cyclopropyl-methoxycarbonyl metomidate: a comparison with propofol.
The pharmacology of cyclopropyl-methoxycarbonyl metomidate: a comparison with propofol.
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DOI：
10.1213/ane.0000000000000069
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发表时间：
2014-03
影响因子：
5.7
通讯作者：
Raines DE
中科院分区：
文献类型：
--
作者：
Ge R;Pejo E;Gallin H;Jeffrey S;Cotten JF;Raines DE
环丙基甲氧羰基美托咪酯（CPMM）是一种“软”依托咪酯类似物，目前正在开发作为丙泊酚的替代品，用于麻醉诱导和维持。我们通过评估CPMM和丙泊酚直接激活α1（L264 T）β3γ2 γ-氨基丁酸A型（GABAA）受体和诱导蝌蚪翻正反射丧失的能力，比较了CPMM和丙泊酚的效力。我们还测量了CPMM和丙泊酚输注后大鼠的脑电图恢复率，持续时间为5至120分钟。CPMM和丙泊酚激活GABAA受体并诱导蝌蚪翻正反射丧失，其半数有效浓度（EC 50）分别为3.8 ± 0.4和3.9 ± 0.2 μM（GABAA受体）和2.6 ± 0.19和1.3 ± 0.04 μM（蝌蚪）。使用CPMM后，长时间输注后的脑电图恢复更快，并且缺乏丙泊酚的背景敏感性。CPMM和丙泊酚在GABAA受体和蝌蚪中具有相似的效力;然而，CPMM比丙泊酚提供更快速和可预测的恢复，特别是在长时间输注后。（Anesth Analg 2014;118：563-7）
Cyclopropyl-methoxycarbonyl metomidate (CPMM) is a “soft” etomidate analogue currently being developed as a propofol alternative for anesthetic induction and maintenance. We compared the potencies of CPMM and propofol by assessing their abilities to directly activate α1(L264T)β3γ2 gamma-aminobutyric acid type A (GABAA) receptors and induce loss of righting reflexes in tadpoles. We also measured the rates of encephalographic recovery in rats after CPMM and propofol infusions ranging in duration from 5 to 120 minutes. CPMM and propofol activate GABAA receptors and induce loss of righting reflexes in tadpoles with respective 50% effective concentrations (EC50s) of 3.8 ± 0.4 and 3.9 ± 0.2 μM (GABAA receptor) and 2.6 ± 0.19 and 1.3 ± 0.04 μM (tadpole). Encephalographic recovery after prolonged infusion was faster with CPMM and lacked propofol’s context sensitivity. CPMM and propofol have similar potencies in GABAA receptors and tadpoles; however, CPMM provides more rapid and predictable recovery than propofol, particularly after prolonged infusion. (Anesth Analg 2014;118:563–7)