Open AccessIn Vivo and In Vitro Pharmacological Studies of Methoxycarbonyl-Carboetomidate
Author(s) -
Ervin Pejo,
Joseph F. Cotten,
Elizabeth Kelly,
Ri Le Ge,
Gregory D. Cuny,
Joydev K. Laha,
Jifeng Liu,
Xiang Lin,
Douglas E. Raines
Publication year - 2012
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/ane.0b013e3182320559
Subject(s) - etomidate , in vivo , ec50 , pharmacology , chromatography , medicine , chemistry , propofol , in vitro , biochemistry , biology , microbiology and biotechnology
We previously developed 2 etomidate analogs that retain etomidate's favorable hemodynamic properties but whose adrenocortical effects are reduced in duration or magnitude. Methoxycarbonyl (MOC)-etomidate is rapidly metabolized and ultrashort acting whereas (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) does not potently inhibit 11β-hydroxylase. We hypothesized that MOC-etomidate's labile ester could be incorporated into carboetomidate to produce a new agent that possesses favorable properties individually found in each agent. We describe the synthesis and pharmacology of MOC-(R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (MOC-carboetomidate), a "soft" analog of carboetomidate.