Cell lines

human embryonic kidney (HEK293) cells (with high expression levels of the cloned murine 2A-adrenoceptor ,α2C-adrenoceptor and α2B -adrenoceptor subtypes)

Preparation method

The solubility of this compound in DMSO is >12.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10μM for 20 min

Applications

In membranes from HEK293 cells transfected with α2-receptors, etomidate inhibited binding of the α2-antagonist, [3H]RX821002, with higher potency from α2B- and α2C-receptors than from α2A-receptors.Etomidate activated mitogen-activated protein kinase phosphorylation via α2B -receptors. In α2B-receptor–expressing HEK293 cells, stimulated with 10μM etomidate for 20 min rapidly increased phosphorylation of the extracellular signal-related kinases ERK1/2.

Animal models

α2Adrenoceptor-deficient Mice, α2Bdrenoceptor-deficient Mice

Dosage form

intraperitoneal injection ,5–50 mg/kg body weight

Application

These results showed that 27% of the mice lost the reflex at 10 mg/kg etomidate and all mice transiently lost the righting reflex at 20mg/kg and higher etomidate doses. After injection of etomidate at 30 mg/kg, the righting reflex disappeared in wild-type and α2 A-deficient mice at similar times after intraperitoneal injection. On intravenous injection of etomidate at 30 mg/kg, wild-type mice showed a rapid and transient hypertensive response that was completely absent in mice lacking α2B-receptors.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Etomidate(R-16659) is a GABAA receptors agonist, which is a short acting intravenous anaesthetic agent used for the induction of general anaesthesia.Target: GABA ReceptorEtomidate is a potent inhibitor of the adrenal response to surgery. The absence of clinical consequences associated with the blunted response suggests that a major increase in adrenal hormone production may not be necessary during surgery [1]. Etomidate is an intravenous induction agent that is associated with hemodynamic stability during intubation. The agent is therefore attractive for use in critically ill patients who have a high risk of hemodynamic instability during this procedure [2]. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality [3].Clinical indications: FDA Approved Date: 1983Toxicity: Undesirable side effects of etomidate that may limit its use include pain on injection, myoclonus and adrenocortical suppression lasting 4-6 hours following an induction dose.

References:
[1]. Griesdale, D.E., Etomidate for intubation of patients who have sepsis or septic shock - where do we go from here Crit Care, 2012. 16(6): p. 189.
[2]. Cherfan, A.J., et al., Etomidate and mortality in cirrhotic patients with septic shock. BMC Clin Pharmacol, 2011. 11: p. 22.
[3]. Mehta, M.P., et al., Etomidate anesthesia inhibits the cortisol response to surgical stress. Acta Anaesthesiol Scand, 1985. 29(5): p. 486-9.