Carboetomidate

Carboetomidate is a pyrrole derivative analogous to the sedative-hypnotic drug Etomidate, which induces general anesthesia while avoiding the inhibition of adrenal steroid synthesis. Carboetomidate enhances GABA_A receptor function via β2/β3 subunits, inhibits neuronal nicotinic acetylcholine receptors (nAChR) and 5-HT₃A receptors, and increases plasma IL-10 levels during endotoxemia. Carboetomidate is applicable to research related to sepsis and sleep disorders^{[1][2][3][4][5][6]}. In Vitro:Carboetomidate potently inhibits human 5-HT₃A receptor function in Tetracycline (HY-A0107)-induced HEK293-TetR cells, with an IC₅₀ of 1.9 µM for integrated current inhibition; this action occurs via reducing peak current amplitude and accelerating receptor desensitization, with significant inhibition observed at its hypnotic concentration^[3].
Carboetomidate accelerates the deactivation rate of human 5-HT₃A receptors in excised outside-out patches from Tetracycline-induced HEK293-TetR cells^[3].
Carboetomidate (10 μM; 90-second pre-perfusion, followed by 90-second co-perfusion with EC_5-10 GABA) potentiates currents mediated by human wild-type α₁β₂γ₂L GABA_A receptors by 390%, but does not potentiate currents mediated by Etomidate-insensitive mutant α₁β₂(M286W)γ₂L GABA_A receptors^[5].
Carboetomidate potently inhibits human α4β2 neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes with an IC₅₀ of 13 μM^[6].
Carboetomidate (48 h) inhibits cortisol synthesis in human adrenocortical carcinoma H295R cells with an IC₅₀ of 2.6 μM^[5].
Carboetomidate (40 μM) produces minimal (2.1%) inhibition of human NR1B/NR2A NMDA receptors expressed in Xenopus laevis oocytes^[6]. In Vivo:Carboetomidate (14 mg/kg; i.v.; single dose) does not alter plasma ACTH, corticosterone, or cytokine responses to LPS-induced endotoxemia in male Sprague-Dawley rats^[2].
Carboetomidate (14 mg/kg; i.v.; every 15 minutes; 8 total doses) does not alter plasma ACTH, corticosterone, TNF-α, IL-1β, or IL-6 responses to LPS-induced endotoxemia, but increases peak plasma IL-10 concentrations to 21 ng/mL in male Sprague-Dawley rats^[2].
Carboetomidate (1-40 μM; immersion; continuous exposure during assessment) is a potent hypnotic in Xenopus laevis tadpoles with an LORR EC₅₀ of 5.4 μM^[5].
Carboetomidate (7-28 mg/kg; i.v.; bolus with saline flush) is a potent hypnotic in adult male Sprague-Dawley rats with an LORR ED₅₀ of 7 mg/kg, a 33 sec onset time at 28 mg/kg, and a dose-dependent LORR duration with a slope of 16 min/(log mg/kg)^[5].
Carboetomidate (14 mg/kg; i.v.; bolus with saline flush) at a hypnotic dose causes minimal hemodynamic changes in adult male Sprague-Dawley rats, with effects comparable to vehicle^[5].
Carboetomidate (14 mg/kg; i.v.; bolus with saline flush) at a hypnotic dose does not suppress adrenocortical function in adult male Sprague-Dawley rats, as evidenced by ACTH_1-24-stimulated serum corticosterone concentrations comparable to vehicle control^[5].