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The pharmacology of cyclopropyl-methoxycarbonyl metomidate: a comparison with propofol
Rile Ge1, Ervin Pejo, Hilary Gallin
1From the *Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital; †Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; and ‡Washington University School of Medicine, St. Louis, Missouri.
Background:
Cyclopropyl-methoxycarbonyl metomidate (CPMM) is a "soft" etomidate analogue currently being developed as a propofol alternative for anesthetic induction and maintenance.
Methods:
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.
Results:
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.
Conclusion:
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.
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