Pharmacological studies of methoxycarbonyl etomidate's carboxylic acid metabolite.
Anesth Analg
; 115(2): 305-8, 2012 Aug.
Article
en En
| MEDLINE
| ID: mdl-22052979
ABSTRACT
BACKGROUND:
Methoxycarbonyl etomidate (MOC-etomidate) is a rapidly metabolized and ultrashort-acting etomidate analog that does not produce prolonged adrenocortical suppression after bolus administration. Its metabolite (MOC-ECA) is a carboxylic acid whose pharmacology is undefined. We hypothesized that MOC-ECA possesses significantly lower pharmacological activity than MOC-etomidate, accounting for the latter's very brief duration of hypnotic action and inability to produce prolonged adrenocortical suppression after bolus administration. To test this hypothesis, we compared the potencies of MOC-ECA and MOC-etomidate in 3 biological assays.METHODS:
The hypnotic potency of MOC-ECA was assessed in tadpoles using a loss-of-righting reflexes assay. The γ-aminobutyric acid type A (GABA(A)) receptor modulatory potencies of MOC-ECA and MOC-etomidate were compared by defining the concentrations of each required to directly activate α(1)(L264T)ß(2)γ(2L) GABA(A) receptors. The adrenocortical inhibitory potencies of MOC-ECA and MOC-etomidate were compared by defining the concentrations of each required to inhibit in vitro cortisol production by adrenocortical cells.RESULTS:
MOC-ECA's 50% effective concentration for loss-of-righting reflexes in tadpoles was 2.8 ± 0.64 mM as compared with a previously reported value of 8 ± 2 µM for MOC-etomidate. The 50% effective concentrations for direct activation of GABA(A) receptors were 3.5 ± 0.63 mM for MOC-ECA versus 10 ± 2.5 µM for MOC-etomidate. The half-maximal inhibitory concentration for inhibiting in vitro cortisol production by adrenocortical cells was 30 ± 7 µM for MOC-ECA versus 0.10 ± 0.02 µM for MOC-etomidate.CONCLUSIONS:
In all 3 biological assays, MOC-ECA's potency was approximately 300-fold lower than that of MOC-etomidate.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Reflejo
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Ácidos Carboxílicos
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Corteza Suprarrenal
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Receptores de GABA-A
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Etomidato
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Agonistas de Receptores de GABA-A
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Hipnóticos y Sedantes
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Anesth Analg
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos