Disease relevance of Hypnomidate

• One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued [1].
• Effect of etomidate on hypercortisolism due to ectopic ACTH production [2].
• It is concluded that many neuroendocrine cell lines, especially those derived from human neuroblastomas, express the NPY gene; the cells display a partly impaired dibasic processing capacity but they generally amidate the products efficiently [3].
• During deep sedation with etomidate, episodes of apnea, hypoxia or arterial hypotension requiring therapeutic intervention did not occur [4].
• Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality [5].

Psychiatry related information on Hypnomidate

• Etomidate-induced convulsion prior to electroconvulsive therapy [6].
• CONCLUSIONS: At concentrations assumed to cause sedation and amnesia, etomidate depresses theta oscillations via beta2-containing GABAA receptors but enhances these oscillations by acting on beta3 subunit containing receptors [7].
• After recovery from etomidate anesthesia, these mice have improved motor performance and less slow wave sleep [8].
• All patients who received both anesthetics for ECT during 2 different episodes had less memory loss during ECT with ketamine than with etomidate [9].
• Patients anesthetized with ketamine for ECT had significantly less impairment of short-term memory function than did patients who received ECT with etomidate anesthesia [9].

High impact information on Hypnomidate

• We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway [1].
• In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450-dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11 beta-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway [1].
• As glucuronides are poorly absorbed from the gut, it is proposed that the hepatic biotransformation of nor-ursodeoxycholate to a glucuronide rather than to a glycine amidate in the liver prevented its accumulation in the bile acid pool [10].
• Etomidate does not suppress PHA-induced growth of normal human lymphocytes [11].
• Here, chimeric beta1/beta2 subunits coexpressed in Xenopus laevis oocytes with human alpha6 and gamma2 subunits identified a region distal to the extracellular N-terminal domain as a determinant of the selectivity of etomidate [12].

Chemical compound and disease context of Hypnomidate

• The effects of the hypnotic agent ethyl phenylethyl imidazole carboxylate (etomidate), on corticosteroidogenesis were studied in greyhound dogs during a 2-h period of anesthetic followed by a further 2 h of anesthetic combined with hemorrhage [13].
• Coadministration of fentanyl and etomidate in order to obtain full anaesthesia and analgesia resulted in respiratory depression [14].
• Pentobarbital protected against hemolysis, whereas etomidate and ketamine promoted hemolysis of erythrocytes [15].
• Adenosine triphosphate, sodium, and potassium concentrations were measured at the end of anoxia in tissue treated with etomidate, propylene glycol, or with no added drugs [16].
• Children with HIV infection, those with a history of adrenal insufficiency, and those submitted to any steroid therapy or etomidate within the week before diagnosis of septic shock were excluded [17].

Biological context of Hypnomidate

• These results suggest that NHA may be activated in TA98 by esterification, and the resulting metabolites may amidate or carbamoylate nucleic acids [18].
• This model also correctly predicts the actions of etomidate on GABA(A) receptors containing a point mutation that increases constitutive gating activity [19].
• OBJECTIVES: The objective of this study was to evaluate the feasibility, safety and efficacy of placing implantable cardioverter-defibrillators (ICDs) in the electrophysiology laboratory using conscious sedation with combined hypnotic agents and deep sedation with etomidate [4].
• These observations suggest that etomidate inhibits mitochondrial cytochrome P450-dependent hydroxylation reactions in the adrenal steroidogenic pathway [20].
• Plasma protein binding of etomidate in patients with renal failure or hepatic cirrhosis [21].

Anatomical context of Hypnomidate

• To identify binding domains in a ligand-gated ion channel for etomidate, an intravenous general anesthetic, we photolabeled nicotinic acetylcholine receptor (nAChR)-rich membranes from Torpedo electric organ with a photoactivatable analog, [(3)H]azietomidate [22].
• We report the emergency and prolonged use of etomidate to control circulating cortisol levels in a patient with Cushing's syndrome secondary to ectopic ACTH production from a pancreatic islet cell tumor [23].
• We show that bovine adrenal chromaffin cells were excited by etomidate at clinically relevant concentrations [24].
• Modulation of [3H]muscimol binding by picrotoxin, pentobarbitone, and etomidate was investigated in rat cerebellar and cerebral cortical membranes [25].
• In 12 dogs we therefore studied (six control and six endotoxin treated, 1.5 mg X kg-1) under etomidate (4 mg X kg-1 X h-1) anaesthesia muscle blood flow (radioactive microspheres) in fore limb, thorax, diaphragm and hind limb (five different muscles) and skin blood flow before (t = 0) and 90 and 120 min after endotoxin [26].

Associations of Hypnomidate with other chemical compounds

• The present investigations were designed to characterize the electrophysiological effects of etomidate on the recurrent GABAergic inhibitory pathway in the CA1 region of the rat in vitro hippocampal slice and to compare the actions of etomidate to those of pentobarbital [27].
• Furthermore, GABA(A) receptors containing the alpha(1)(G223F) point mutation also significantly decreased the maximal effect of etomidate- and propofol-induced enhancement of ligand binding [28].
• The effects of subunit composition of the gamma-aminobutyric acid (GABA) type A receptor on the multiple actions of the general anesthetics alphaxalone and etomidate were investigated [29].
• Block of alpha1G current by anesthetics had the following order of potency: propofol (IC(50) approximately 20.5 microM) > etomidate ( approximately 161 microM) = octanol ( approximately 160 microM) > isoflurane ( approximately 277 microM) > ketamine ( approximately 1.2 mM), comparable with results on DRG T currents [30].
• Differential subunit dependence of the actions of the general anesthetics alphaxalone and etomidate at gamma-aminobutyric acid type A receptors expressed in Xenopus laevis oocytes [29].

Gene context of Hypnomidate

• In alpha2B-receptor-expressing HEK293 cells, etomidate rapidly increased phosphorylation of the extracellular signal-related kinases ERK1/2 [31].
• RESULTS: In vivo, loss and recovery of the righting reflex required similar times after intraperitoneal injection of etomidate in wild-type and in alpha2A-receptor-deficient mice, indicating that the hypnotic effect of etomidate in mice does not require the alpha2A-receptor subtype [31].
• CONCLUSIONS: The GABAA receptor beta 2 subunit mediates a significant proportion of the hypothermic effects of etomidate [8].
• During the infusion of etomidate, a significant increase in the peripheral concentration of ACTH occurred, while plasma cortisol concentrations decreased [32].
• Cytochrome P-450 binding spectra displayed type II binding with a UV light absorption maximum (lambda max) at a wavelength of 424 nm in the presence of etomidate [33].

Analytical, diagnostic and therapeutic context of Hypnomidate

• Etomidate in the intensive care unit [34].
• CONCLUSIONS: Implantation of ICDs under conscious sedation with combined hypnotic agents and deep sedation with etomidate is a safe and effective procedure with low perioperative morbidity and low long-term complication rates [4].
• Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system [35].
• Etomidate produced progressive slowing of the EEG to an easily recognized pattern (stage 3) that determined the dosage endpoint [36].
• A supratherapeutic dose of etomidate was used to test the hypothesis that the bronchoconstrictive response could be minimized by deep intravenous anesthesia [37].

References