Anesthesia & Analgesia 2014-03-01

The pharmacology of cyclopropyl-methoxycarbonyl metomidate: a comparison with propofol.

Rile Ge, Ervin Pejo, Hilary Gallin, Spencer Jeffrey, Joseph F Cotten, Douglas E Raines

Index: Anesth. Analg. 118(3) , 563-7, (2014)

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Abstract

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.