Clinical and molecular pharmacology of etomidate

Anesthesiology

Volumn 114, Issue 3, 2011, Pages 695-707

  Forman, Stuart A ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ALDOSTERONE; ALTHESIN; BENZODIAZEPINE; CORTICOSTEROID; CORTISONE; CORTODOXONE; DEOXYCORTICOSTERONE; ETOMIDATE; HYDROCORTISONE; HYDROXYPROGESTERONE; KETAMINE; METHOHEXITAL; OPIATE; PENTOBARBITAL; PROGESTERONE; PROPOFOL; THIOPENTAL;

ADRENAL DISEASE; ADRENAL GLAND TOXICITY; ALDOSTERONE BLOOD LEVEL; AMNESIA; ANESTHESIA INDUCTION; ANTINOCICEPTION; APNEA; CENTRAL NERVOUS SYSTEM; CHEMOSENSITIVITY; CONTINUOUS INFUSION; CRITICALLY ILL PATIENT; DRUG BINDING SITE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG SOLUBILITY; DRUG STABILITY; DRUG STRUCTURE; ELECTROCONVULSIVE THERAPY; EPILEPSY; EVOKED MUSCLE RESPONSE; EVOKED SOMATOSENSORY RESPONSE; GENERAL ANESTHESIA; HORMONE SYNTHESIS; HUMAN; HYDROCORTISONE BLOOD LEVEL; HYDROPHOBICITY; HYPNOSIS; LD 50; NONHUMAN; PKA; POINT MUTATION; POSTOPERATIVE NAUSEA AND VOMITING; PRIORITY JOURNAL; PROGESTERONE BLOOD LEVEL; PROTEIN DOMAIN; PROTEIN EXPRESSION; REVIEW; RIGHTING REFLEX; SEDATION; SIDE EFFECT; SINGLE DRUG DOSE; STEREOCHEMISTRY; SURVIVAL; TRANSGENIC ANIMAL;

EID: 79952043405     PISSN: 00033022     EISSN: 15281175     Source Type: Journal    
DOI: 10.1097/ALN.0b013e3181ff72b5     Document Type: Review

References (160)

1. Godefroi EF, Janssen PAJ, Van der Eycken CAM, Van Heertum AHMT, Niemegeers CJE: DL-(1-arylalkyl)imidazole-5-carboxylate esters: A novel type of hypnotic agents. J Med Chem 1965; 56:220-3
2. Tomlin SL, Jenkins A, Lieb WR, Franks NP: Stereoselective effects of etomidate optical isomers on γ-aminobutyric acid type A receptors and animals. ANESTHESIOLOGY 1998; 88:708-17 (Pubitemid 28120205)
3. Husain SS, Ziebell MR, Ruesch D, Hong F, Arevalo E, Kosterlitz JA, Olsen RW, Forman SA, Cohen JB, Miller KW: 2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: A derivative of the stereoselective general anesthetic etomidate for photolabeling ligand-gated ion channels. J Med Chem 2003; 46:1257-65 (Pubitemid 36428231)
4. Janssen PA, Niemegeers CJ, Schellekens KH, Lenaerts FM: Etomidate, R-(+)-ethyl-1-(-methyl-benzyl)imidazole-5-carboxylate (R 16659), a potent, short-acting and relatively atoxic intravenous hypnotic agent in rats. Arzneimittelforschung 1971; 21:1234-43
5. Janssen PA, Niemegeers CJ, Marsboom RP: Etomidate, a potent non-barbiturate hypnotic. Intravenous etomidate in mice, rats, guinea-pigs, rabbits and dogs. Arch Int Pharmacodyn Ther 1975; 214:92-132
6. Doenicke A, Wagner E, Beetz KH: Arterial blood gas analyses following administration of three short-acting i.v. hypnotics (propanidid, etomidate, methohexitone). Anaesthesist 1973; 22:353-6
7. Morgan M, Lumley J, Whitwam JG: Etomidate, a new water-soluble non-barbiturate intravenous induction agent. Lancet 1975; 321:955-6
8. Doenicke A, Roizen MF, Hoernecke R, Mayer M, Ostwald P, Foss J: Haemolysis after etomidate: Comparison of propylene glycol and lipid formulations. Br J Anaesth 1997; 79:386-8 (Pubitemid 27404058)
9. Doenicke A, Roizen MF, Nebauer AE, Kugler A, Hoernecke R, Beger-Hintzen H: A comparison of two formulations for etomidate, 2-hydroxypropyl-beta- cyclodextrin (HPCD) and propylene glycol. Anesth Analg 1994; 79:933-9 (Pubitemid 24324674)
10. McIntosh MP, Schwarting N, Rajewski RA: In vitro and in vivo evaluation of a sulfobutyl ether beta-cyclodextrin enabled etomidate formulation. J Pharm Sci 2004; 93:2585-94
11. Kay B: Total intravenous anesthesia with etomidate. II. Evaluation of a practical technique for children. Acta Anaesthesiol Belg 1977; 28:115-21
12. Scorgie B: Etomidate infusion. Its use in anaesthesia for general surgery. Anaesthesia 1983; 38(suppl):63-5
13. Fruergaard K, Jenstrup M, Schierbeck J, Wiberg-Jørgensen F: Total intravenous anaesthesia with propofol or etomidate. Eur J Anaesthesiol 1991; 8:385-91
14. Streisand JB, Jaarsma RL, Gay MA, Badger MJ, Maland L, Nordbrock E, Stanley TH: Oral transmucosal etomidate in volunteers. ANESTHESIOLOGY 1998; 88:89-95 (Pubitemid 28053259)
15. Linton DM, Thornington RE: Etomidate as a rectal induction agent. Part II. A clinical study in children. S Afr Med J 1983; 64:309-10
16. Latson TW, McCarroll SM, Mirhej MA, Hyndman VA, Whitten CW, Lipton JM: Effects of three anesthetic induction techniques on heart rate variability. J Clin Anesth 1992; 4:265-76
17. Gelissen HP, Epema AH, Henning RH, Krijnen HJ, Hennis PJ, den Hertog A: Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle. ANESTHESIOLOGY 1996; 84:397-403 (Pubitemid 26053841)
18. du Cailar J, Béssou D, Griffe O, Kienlen J: Hemodynamic effects of etomidate. Ann Anesthesiol Fr 1976; 17:1223-7
19. Criado A, Maseda J, Navarro E, Escarpa A, Avello F: Induction of anaesthesia with etomidate: Haemodynamic study of 36 patients. Br J Anaesth 1980; 52:803-6 (Pubitemid 10090449)
20. Ebert TJ, Muzi M, Berens R, Goff D, Kampine JP: Sympathetic responses to induction of anesthesia in humans with propofol or etomidate. ANESTHESIOLOGY 1992; 76:725-33
21. Giese JL, Stockham RJ, Stanley TH, Pace NL, Nelissen RH: Etomidate versus thiopental for induction of anesthesia. Anesth Analg 1985; 64:871-6
22. Stockham RJ, Stanley TH, Pace NL, Gillmor S, Groen F, Hilkens P: Fentanyl pretreatment modifies anaesthetic induction with etomidate. Anaesth Intensive Care 1988; 16:171-6
23. Bovill JG: Intravenous anesthesia for the patient with left ventricular dysfunction. Semin Cardiothorac Vasc Anesth 2006; 10:43-8
24. Johnson KB, Egan TD, Layman J, Kern SE, White JL, McJames SW: The influence of hemorrhagic shock on etomidate: A pharmacokinetic and pharmacodynamic analysis. Anesth Analg 2003; 96:1360-8 (Pubitemid 36512876)
25. Johnson KB, Egan TD, Kern SE, McJames SW, Cluff ML, Pace NL: Influence of hemorrhagic shock followed by crystalloid resuscitation on propofol: A pharmacokinetic and pharmacodynamic analysis. ANESTHESIOLOGY 2004; 101:647-59 (Pubitemid 39121644)
26. Shafer SL: Shock values. ANESTHESIOLOGY 2004; 101:567-8
27. Sakles JC, Laurin EG, Rantapaa AA, Panacek EA: Airway management in the emergency department: A one-year study of 610 tracheal intubations. Ann Emerg Med 1998; 31:325-32 (Pubitemid 28135355)
28. Zuckerbraun NS, Pitetti RD, Herr SM, Roth KR, Gaines BA, King C: Use of etomidate as an induction agent for rapid sequence intubation in a pediatric emergency department. Acad Emerg Med 2006; 13:602-9 (Pubitemid 43744545)
29. Zed PJ, Mabasa VH, Slavik RS, Abu-Laban RB: Etomidate for rapid sequence intubation in the emergency department: Is adrenal suppression a concern? Clin J Emerg Med 2006; 8:347-50 (Pubitemid 44608321)
30. Van Hamme MJ, Ghoneim MM, Ambre JJ: Pharmacokinetics of etomidate, a new intravenous anesthetic. ANESTHESIOLOGY 1978; 49:274-7 (Pubitemid 9032541)
31. Atiba JO, Horai Y, White PF, Trevor AJ, Blaschke TF, Sung ML: Effect of etomidate on hepatic drug metabolism in humans. ANESTHESIOLOGY 1988; 68:920-4
32. Cold GE, Eskesen V, Eriksen H, Amtoft O, Madsen JB: CBF and CMRO2 during continuous etomidate infusion supplemented with N2O and fentanyl in patients with supratentorial cerebral tumour. A dose-response study. Acta Anaesthesiol Scand 1985; 29:490-4 (Pubitemid 15047424)
33. Van Aken J, Rolly G: Influence of etomidate, a new short acting anesthetic agent, on cerebral blood flow in man. Acta Anaesthesiol Belg 1976; 27(suppl):175-80
34. Batjer HH: Cerebral protective effects of etomidate: Experimental and clinical aspects. Cerebrovasc Brain Metab Rev 1993; 5:17-32
35. Ghoneim MM, Yamada T: Etomidate: A clinical and electroencephalographic comparison with thiopental. Anesth Analg 1977; 56:479-85 (Pubitemid 8159466)
36. Lallemand MA, Lentschener C, Mazoit JX, Bonnichon P, Manceau I, Ozier Y: Bispectral index changes following etomidate induction of general anaesthesia and orotracheal intubation. Br J Anaesth 2003; 91:341-6 (Pubitemid 37063348)
37. Kaneda K, Yamashita S, Woo S, Han TH: Population pharmacokinetics pharmacodynamics of brief etomidate infusion in healthy volunteers [published online ahead of print May 24, 2010]. J Clin Pharmacol, doi: 10.1177/ 0091270010369242
38. Thornton C, Heneghan CP, Navaratnarajah M, Bateman PE, Jones JG: Effect of etomidate on the auditory evoked response in man. Br J Anaesth 1985; 57:554-61 (Pubitemid 15058083)
39. Ding Z, White PF: Anesthesia for electroconvulsive therapy. Anesth Analg 2002; 94:1351-64 (Pubitemid 34441865)
40. Sloan TB, Ronai AK, Toleikis JR, Koht A: Improvement of intraoperative somatosensory evoked potentials by etomidate. Anesth Analg 1988; 67:582-5
41. Taniguchi M, Nadstawek J, Langenbach U, Bremer F, Schramm J: Effects of four intravenous anesthetic agents on motor evoked potentials elicited by magnetic transcranial stimulation. Neurosurgery 1993; 33:407-15 (Pubitemid 23260747)
42. Carlos R, Calvo R, Erill S: Plasma protein binding of etomidate in patients with renal failure or hepatic cirrhosis. Clin Pharmacokinet 1979; 4:144-8 (Pubitemid 9146084)
43. Giese JL, Stanley TH: Etomidate: A new intravenous anesthetic induction agent. Pharmacotherapy 1983; 3:251-8 (Pubitemid 14243378)
44. Heykants JJP, Brugmans J, Doenicke A: On the pharmacokinetics of etomidate (R26490) in human volunteers: Plasma levels, metabolism, and excretion. (R26490/1 Janssen Research Product Information Service), Clinical Research Report 1975
45. Arden JR, Holley FO, Stanski DR: Increased sensitivity to etomidate in the elderly: Initial distribution versus altered brain response. ANESTHESIOLOGY 1986; 65:19-27 (Pubitemid 16098088)
46. Carlos R, Calvo R, Erill S: Plasma protein binding of etomidate in different age groups and in patients with chronic respiratory insufficiency. Int J Clin Pharmacol Ther Toxicol 1981; 19:171-4 (Pubitemid 11096802)
47. Sear J: Total intravenous anesthesia, Anesthesiology, 1st edition. Edited by Longnecker DE, Brown DL, Newman MF, Zapol WM. New York, McGraw Hill Medical, 2008, pp 897-917
48. Kay B: Total intravenous anesthesia with etomidate. I. A trial in children. Acta Anaesthesiol Belg 1977; 28:107-13
49. van de Walle J, Demeyere R, Vanacker B, Vermaut G, Vandermeersch E: Total I.V. anesthesia using a continuous etomidate infusion. Acta Anaesthesiol Belg 1979; 30(suppl):117-22 (Pubitemid 10084415)
50. van Oss GE, Rachmat Y, Booij LH, Crul JF: Continuous infusion of etomidate as a method for outpatient anesthesia. Acta Anaesthesiol Belg 1980; 31:39-43 (Pubitemid 10033305)
51. Edbrooke DL, Newby DM, Mather SJ, Dixon AM, Hebron BS: Safer sedation for ventilated patients. A new application for etomidate. Anaesthesia 1982; 37:765-71
52. Bird TM, Edbrooke DL, Newby DM, Hebron BS: Intravenous sedation for the intubated and spontaneously breathing patient in the intensive care unit. Acta Anaesthesiol Scand 1984; 28:640-3 (Pubitemid 15179557)
53. Kay B: Some experience of the use of etomidate in children. Acta Anaesthesiol Belg 1976; 27(suppl):86-92
54. Kay B, Rolly G: Total intravenous anesthesia with etomidate. III. Some observations in adults. Acta Anaesthesiol Belg 1977; 28:157-64
55. Yelavich PM, Holmes CM: Etomidate: A foreshortened clinical trial. Anaesth Intensive Care 1980; 8:479-83 (Pubitemid 11234022)
56. Zacharias M, Clarke RS, Dundee JW, Johnston SB: Evaluation of three preparations of etomidate. Br J Anaesth 1978; 50:925-9 (Pubitemid 9063441)
57. Nyman Y, Von Hofsten K, Palm C, Eksborg S, Lönnqvist PA: Etomidate-lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine. Br J Anaesth 2006; 97:536-9 (Pubitemid 44419969)
58. Doenicke AW, Roizen MF, Kugler J, Kroll H, Foss J, Ostwald P: Reducing myoclonus after etomidate. ANESTHESIOLOGY 1999; 90:113-9
59. Hwang JY, Kim JH, Oh AY, Do SH, Jeon YT, Han SH: A comparison of midazolam with remifentanil for the prevention of myoclonic movements following etomidate injection. J Int Med Res 2008; 36:17-22
60. Mizrak A, Koruk S, Bilgi M, Kocamer B, Erkutlu I, Ganidagli S, Oner U: Pretreatment with dexmedetomidine or thiopental decreases myoclonus after etomidate: A randomized, double-blind controlled trial. J Surg Res 2010; 159:e11-6
61. Zacharias M, Dundee JW, Clarke RS, Hegarty JE: Effect of preanaesthetic medication on etomidate. Br J Anaesth 1979; 51:127-33 (Pubitemid 10198383)
62. Helmers JH, Adam AA, Giezen J: Pain and myoclonus during induction with etomidate. A double-blind, controlled evaluation of the influence of droperidol and fentanyl. Acta Anaesthesiol Belg 1981; 32:141-7
63. Ulsamer B, Doenicke A, Laschat M: Propofol in comparison with etomidate for the induction of anesthesia. Anaesthesist 1986; 35:535-42 (Pubitemid 16012213)
64. Mayer M, Doenicke A, Nebauer AE, Hepting L: Propofol and etomidate-lipuro for induction of general anesthesia. Hemodynamics, vascular compatibility, subjective findings and postoperative nausea. Anaesthesist 1996; 45:1082-4
65. St Pierre M, Dunkel M, Rutherford A, Hering W: Does etomidate increase postoperative nausea? A double-blind controlled comparison of etomidate in lipid emulsion with propofol for balanced anaesthesia. Eur J Anaesthesiol 2000; 17:634-41
66. Ledingham IM, Watt I: Influence of sedation on mortality in critically ill multiple trauma patients. Lancet 1983; 321:1270
67. Watt I, Ledingham IM: Mortality amongst multiple trauma patients admitted to an intensive therapy unit. Anaesthesia 1984; 39:973-81 (Pubitemid 15076641)
68. McKee JI, Finlay WE: Cortisol replacement in severely stressed patients. Lancet 1983; 321:484 (Pubitemid 13137402)
69. Preziosi P, Vacca M: Etomidate and corticotrophic axis. Arch Int Pharmacodyn Ther 1982; 256:308-10 (Pubitemid 12136233)
70. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D: Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 1984; 310:1415-21 (Pubitemid 14101296)
71. Wagner RL, White PF: Etomidate inhibits adrenocortical function in surgical patients. ANESTHESIOLOGY 1984; 61:647-51 (Pubitemid 15223411)
72. Fragen RJ, Shanks CA, Molteni A, Avram MJ: Effects of etomidate on hormonal responses to surgical stress. ANESTHESIOLOGY 1984; 61:652-6 (Pubitemid 15223412)
73. Allolio B, Stuttmann R, Leonhard U, Fischer H, Winkelmann W: Adrenocortical suppression by a single induction dose of etomidate. Klin Wochenschr 1984; 62:1014-7
74. Wanscher M, Tønnesen E, Hüttel M, Larsen K: Etomidate infusion and adrenocortical function. A study in elective surgery. Acta Anaesthesiol Scand 1985; 29:483-5
75. Editorial: Etomidate. Lancet 1983; 322:24-5
76. Longnecker DE: Stress free: To be or not to be? ANESTHESIOLOGY 1984; 61:643-4
77. Owen H, Spence AA: Etomidate. Br J Anaesth 1984; 56:555-7 (Pubitemid 14083280)
78. Diago MC, Amado JA, Otero M, Lopez-Cordovilla JJ: Anti-adrenal action of a subanaesthetic dose of etomidate. Anaesthesia 1988; 43:644-5
79. Zolle IM, Berger ML, Hammerschmidt F, Hahner S, Schirbel A, Peric-Simov B: New selective inhibitors of steroid 11beta-hydroxylation in the adrenal cortex. Synthesis and structure-activity relationship of potent etomidate analogues. J Med Chem 2008; 51:2244-53 (Pubitemid 351503279)
80. Annane D, Sébille V, Charpentier C, Bollaert PE, François B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troché G, Chaumet-Riffaud P, Bellissant E: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288:862-71
81. Annane D, Sebille V: Corticosteroids for patients with septic shock. JAMA 2003; 289:43-4
82. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J, CORTICUS Study Group: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358:111-24
83. Mohammad Z, Afessa B, Finkielman JD: The incidence of relative adrenal insufficiency in patients with septic shock after the administration of etomidate. Crit Care 2006; 10:R105
84. Lipiner-Friedman D, Sprung CL, Laterre PF, Weiss Y, Goodman SV, Vogeser M, Briegel J, Keh D, Singer M, Moreno R, Bellissant E, Annane D: Adrenal function in sepsis: The retrospective Corticus cohort study. Crit Care Med 2007; 35:1012-8 (Pubitemid 46598949)
85. Cuthbertson BH, Sprung CL, Annane D, Chevret S, Garfield M, Goodman S, Laterre PF, Vincent JL, Freivogel K, Reinhart K, Singer M, Payen D, Weiss YG: The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock. Intensive Care Med 2009; 35:1868-76
86. Vinclair M, Broux C, Faure P, Brun J, Genty C, Jacquot C, Chabre O, Payen JF: Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med 2008; 34:714-9 (Pubitemid 351660088)
87. Absalom A, Pledger D, Kong A: Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 1999; 54:861-7 (Pubitemid 29415418)
88. den Brinker M, Hokken-Koelega AC, Hazelzet JA, de Jong FH, Hop WC, Joosten KF: One single dose of etomidate negatively influences adrenocortical performance for at least 24 h in children with meningococcal sepsis. Intensive Care Med 2008; 34:163-8
89. Hildreth AN, Mejia VA, Maxwell RA, Smith PW, Dart BW, Barker DE: Adrenal suppression following a single dose of etomidate for rapid sequence induction: A prospective randomized study. J Trauma 2008; 65:573-9
90. Tekwani KL, Watts HF, Rzechula KH, Sweis RT, Kulstad EB: A prospective observational study of the effect of etomidate on septic patient mortality and length of stay. Acad Emerg Med 2009; 16:11-4
91. Ray DC, McKeown DW: Effect of induction agent on vasopressor and steroid use, and outcome in patients with septic shock. Crit Care 2007; 11:R56
92. Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, Bertrand L, Beltramini A, Gamand P, Albizzati S, Perdrizet D, Lebail G, Chollet-Xemard C, Maxime V, Brun-Buisson C, Lefrant JY, Bollaert PE, Megarbane B, Ricard JD, Anguel N, Vicaut E, Adnet F, KETASED Collaborative Study Group: Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: A multicentre randomised controlled trial. Lancet 2009; 374:293-300
93. Jackson WL Jr: Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock? A critical appraisal. Chest 2005; 127:1031-8
94. Walls RM, Murphy MF: Clinical controversies: Etomidate as an induction agent for endotracheal intubation in patients with sepsis: Continue to use etomidate for intubation of patients with septic shock. Ann Emerg Med 2008; 52:13-4 (Pubitemid 351815151)
95. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci 1999; 55:1278-303 (Pubitemid 29410747)
96. Rudolph U, Antkowiak B: Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 2004; 5:709-20 (Pubitemid 39150142)
97. Evans RH, Hill RG: GABA-mimetic action of etomidate. Experientia 1978; 34:1325-7 (Pubitemid 9040107)
98. Carlson BX, Hales TG, Olsen RW: GABA-A receptors and anesthesia, Anesthesia Biologic Foundations. Edited by Yaksh TL, Lynch C, Zapol WM, Maze M, Biebuyck JF, Saidman LJ. Philadelphia, Lippincott-Raven, 1998, pp 259-76
99. Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, Sixma TK: Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 2001; 411:269-76 (Pubitemid 32467026)
100. Unwin N: Refined structure of the nicotinic acetylcholine receptor at 4A resolution. J Mol Biol 2005; 346:967-89
101. Bocquet N, Nury H, Baaden M, Le Poupon C, Changeux JP, Delarue M, Corringer PJ: X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 2009; 457:111-4
102. Hilf RJ, Dutzler R: Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature 2009; 457:115-8
103. Hilf RJ, Dutzler R: X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 2008; 452:375-9 (Pubitemid 351430790)
104. Olsen RW, Sieghart W: GABA(A) receptors: Subtypes provide diversity of function and pharmacology. Neuropharmacology 2008; 56:141-8
105. Baumann SW, Baur R, Sigel E: Subunit arrangement of gamma-aminobutyric acid type A receptors. J Biol Chem 2001; 276:36275-80
106. McKernan RM, Whiting PJ: Which GABAA-receptor subtypes really occur in the brain? Trends Neurosci 1996; 19:139-43
107. Segal M, Barker JL: Rat hippocampal neurons in culture: Voltage-clamp analysis of inhibitory synaptic connections. J Neurophysiol 1984; 52:469-87 (Pubitemid 14034164)
108. Vierling-Claassen D, Siekmeier P, Stufflebeam S, Kopell N: Modeling GABA alterations in schizophrenia: A link between impaired inhibition and altered gamma and beta range auditory entrainment. J Neurophysiol 2008; 99:2656-71
109. Whittington MA, Traub RD, Kopell N, Ermentrout B, Buhl EH: Inhibition-based rhythms: Experimental and mathematical observations on network dynamics. Int J Psychophysiol 2000; 38:315-36
110. Banks MI, Pearce RA: Kinetic differences between synaptic and extrasynaptic GABA(A) receptors in CA1 pyramidal cells. J Neurosci 2000; 20:937-48 (Pubitemid 30220450)
111. Herd MB, Belelli D, Lambert JJ: Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors. Pharmacol Ther 2007; 116:20-34 (Pubitemid 47391030)
112. Sem'yanov AV: Diffusional extrasynaptic neurotransmission via glutamate and GABA. Neurosci Behav Physiol 2005; 35:253-66
113. Uchida I, Kamatchi G, Burt D, Yang J: Etomidate potentiation of GABAA receptor gated current depends on the subunit composition. Neurosci Lett 1995; 185:203-6
114. Rüsch D, Zhong H, Forman SA: Gating allosterism at a single class of etomidate sites on alpha1beta2gamma2L GABA-A receptors accounts for both direct activation and agonist modulation. J Biol Chem 2004; 279:20982-92 (Pubitemid 38656498)
115. Yang J, Uchida I: Mechanisms of etomidate potentiation of GABAA receptor-gated currents in cultured postnatal hippocampal neurons. Neuroscience 1996; 73:69-78
116. Zhong H, Rüsch D, Forman SA: Photo-activated azi-etomidate, a general anesthetic photolabel, irreversibly enhances gating and desensitization of γ-aminobutyric acid type A receptors. ANESTHESIOLOGY 2008; 108:103-12
117. Hill-Venning C, Belelli D, Peters JA, Lambert JJ: Subunit-dependent interaction of the general anaesthetic etomidate with the gamma-aminobutyric acid type A receptor. Br J Pharmacol 1997; 120:749-56
118. Ashton D, Wauquier A: Modulation of a GABA-ergic inhibitory circuit in the in vitro hippocampus by etomidate isomers. Anesth Analg 1985; 64:975-80
119. A receptor in general anaesthesia. Neuropharmacology 2003; 45:57-71
120. Sanna E, Murgia A, Casula A, Biggio G: 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. Mol Pharmacol 1997; 51:484-90 (Pubitemid 27118485)
121. Belelli D, Lambert JJ, Peters JA, Wafford K, Whiting PJ: The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid. Proc Nat Acad Sci USA 1997; 94:11031-6
122. McGurk KA, Pistis M, Belelli D, Hope AG, Lambert JJ: The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor. Br J Pharmacol 1998; 124:13-20 (Pubitemid 28210037)
123. Siegwart R, Jurd R, Rudolph U: Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3)gamma(2)gamma-aminobutyric acid(A) receptors. J Neurochem 2002; 80:140-8
124. Siegwart R, Krahenbuhl K, Lambert S, Rudolph U: Mutational analysis of molecular requirements for the actions of general anaesthetics at the gamma-aminobutyric acidA receptor subtype, alpha1beta2gamma2. BMC Pharmacol 2003; 3:13
125. Desai R, Ruesch D, Forman SA: γ-Aminobutyric acid type A receptor mutations at β2N265 alter etomidate efficacy while preserving basal and agonist-dependent activity. ANESTHESIOLOGY 2009; 111:774-84
126. Krasowski MD, Koltchine VV, Rick CE, Ye Q, Finn SE, Harrison NL: Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane. Mol Pharmacol 1998; 53:530-8 (Pubitemid 28162877)
127. Stewart D, Desai R, Cheng Q, Liu A, Forman SA: Tryptophan mutations at azi-etomidate photo-incorporation sites on alpha1 or beta2 subunits enhance GABAA receptor gating and reduce etomidate modulation. Mol Pharmacol 2008; 74:1687-95
128. Jurd R, Arras M, Lambert S, Drexler B, Siegwart R, Crestani F, Zaugg M, Vogt KE, Ledermann B, Antkowiak B, Rudolph U: General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J 2003; 17:250-2
129. Reynolds DS, Rosahl TW, Cirone J, O'Meara GF, Haythornthwaite A, Newman RJ, Myers J, Sur C, Howell O, Rutter AR, Atack J, Macaulay AJ, Hadingham KL, Hutson PH, Belelli D, Lambert JJ, Dawson GR, McKernan R, Whiting PJ, Wafford KA: Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms. J Neurosci 2003; 23:8608-17 (Pubitemid 37158760)
130. Cirone J, Rosahl TW, Reynolds DS, Newman RJ, O'Meara GF, Hutson PH, Wafford KA: γ-Aminobutyric acid type A receptor β2 subunit mediates the hypothermic effect of etomidate in mice. ANESTHESIOLOGY 2004; 100:1438-45 (Pubitemid 38679313)
131. Herd MB, Haythornthwaite AR, Rosahl TW, Wafford KA, Homanics GE, Lambert JJ, Belelli D: The expression of GABAA beta subunit isoforms in synaptic and extrasynaptic receptor populations of mouse dentate gyrus granule cells. J Physiol 2008; 586:989-1004 (Pubitemid 351267341)
132. Cheng VY, Martin LJ, Elliott EM, Kim JH, Mount HT, Taverna FA, Roder JC, Macdonald JF, Bhambri A, Collinson N, Wafford KA, Orser BA: Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J Neurosci 2006; 26:3713-20
133. Mihalek RM, Banerjee PK, Korpi ER, Quinlan JJ, Firestone LL, Mi ZP, Lagenaur C, Tretter V, Sieghart W, Anagnostaras SG, Sage JR, Fanselow MS, Guidotti A, Spigelman I, Li Z, DeLorey TM, Olsen RW, Homanics GE: Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice. Proc Natl Acad Sci U S A 1999; 96:12905-10 (Pubitemid 29513601)
134. Bright DP, Adham SD, Lemaire LC, Benavides R, Gruss M, Taylor GW, Smith EH, Franks NP: Identification of anesthetic binding sites on human serum albumin using a novel etomidate photolabel. J Biol Chem 2007; 282:12038-47 (Pubitemid 47100674)
135. Liao M, Sonner JM, Husain SS, Miller KW, Jurd R, Rudolph U, Eger EI 2nd: R (+) etomidate and the photoactivable R (+) azietomidate have comparable anesthetic activity in wild-type mice and comparably decreased activity in mice with a N265M point mutation in the γ-aminobutyric acid receptor beta3 subunit. Anesth Analg 2005; 101:131-5 (Pubitemid 40853363)
136. Li GD, Chiara DC, Sawyer GW, Husain SS, Olsen RW, Cohen JB: Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog. J Neurosci 2006; 26:11599-605 (Pubitemid 44772131)
137. Bali M, Jansen M, Akabas MH: GABA-induced intersubunit conformational movement in the GABAA receptor alpha1M1-beta2M3 transmembrane subunit interface: Experimental basis for homology modeling of an intravenous anesthetic binding site. J Neurosci 2009; 29:3083-92
138. Jenkins A, Greenblatt EP, Faulkner HJ, Bertaccini E, Light A, Lin A, Andreasen A, Viner A, Trudell JR, Harrison NL: Evidence for a common binding cavity for three general anesthetics within the GABAA receptor. J Neurosci 2001; 21:RC136
139. Dörr HG, Kuhnle U, Holthausen H, Bidlingmaier F, Knorr D: Etomidate: A selective adrenocortical 11 beta-hydroxylase inhibitor. Klin Wochenschr 1984; 62:1011-3 (Pubitemid 14017346)
140. Varga I, Rácz K, Kiss R, Fütö L, Tóth M, Sergev O, Gláz E: Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells. Steroids 1993; 58:64-8
141. Mornet E, Dupont J, Vitek A, White PC: Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta). J Biol Chem 1989; 264:20961-7 (Pubitemid 20017902)
142. Ullerås E, Ohlsson A, Oskarsson A: Secretion of cortisol and aldosterone as a vulnerable target for adrenal endocrine disruption: Screening of 30 selected chemicals in the human H295R cell model. J Appl Toxicol 2008; 28:1045-53
143. Poulos TL, Howard AJ: Crystal structures of metyrapone- and phenylimidazole-inhibited complexes of cytochrome P-450cam. Biochemistry 1987; 26:8165-74 (Pubitemid 18023065)
144. Gay SC, Sun L, Maekawa K, Halpert JR, Stout CD: Crystal structures of cytochrome P450 2B4 in complex with the inhibitor 1-biphenyl-4-methyl-1H- imidazole: Ligand-induced structural response through alpha-helical repositioning. Biochemistry 2009; 48:4762-71
145. Ouellet H, Podust LM, de Montellano PR: Mycobacterium tuberculosis CYP130: Crystal structure, biophysical characterization, and interactions with antifungal azole drugs. J Biol Chem 2008; 283:5069-80
146. Zöllner A, Kagawa N, Waterman MR, Nonaka Y, Takio K, Shiro Y, Hannemann F, Bernhardt R: Purification and functional characterization of human 11beta hydroxylase expressed in Escherichia coli. FEBS J 2008; 275:799-810 (Pubitemid 351160976)
147. Roumen L, Sanders MP, Pieterse K, Hilbers PA, Plate R, Custers E, de Gooyer M, Smits JF, Beugels I, Emmen J, Ottenheijm HC, Leysen D, Hermans JJ: Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics. J Comput Aided Mol Des 2007; 21:455-71 (Pubitemid 47423278)
148. Paris A, Philipp M, Tonner PH, Steinfath M, Lohse M, Scholz J, Hein L: Activation of α2B-adrenoceptors mediates the cardiovascular effects of etomidate. ANESTHESIOLOGY 2003; 99:889-95 (Pubitemid 37186080)
149. Alkire MT, Hudetz AG, Tononi G: Consciousness and anesthesia. Science 2008; 322:876-80
150. Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP: General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc Natl Acad Sci USA 2008; 105:8784-9 (Pubitemid 351987757)
151. Hahner S, Stuermer A, Kreissl M, Reiners C, Fassnacht M, Haenscheid H, Beuschlein F, Zink M, Lang K, Allolio B, Schirbel A: [123 I]iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes. J Clin Endocrinol Metab 2008; 93:2358-65 (Pubitemid 351831559)
152. Igaz P, Tömböl Z, Szabó PM, Likó I, Rácz K: Steroid biosynthesis inhibitors in the therapy of hypercortisolism: Theory and practice. Curr Med Chem 2008; 15:2734-47
153. Schulte HM, Benker G, Reinwein D, Sippell WG, Allolio B: Infusion of low dose etomidate: Correction of hypercortisolemia in patients with Cushing's syndrome and doseresponse relationship in normal subjects. J Clin Endocrinol Metab 1990; 70:1426-30
154. Fassnacht M, Hahner S, Beuschlein F, Klink A, Reincke M, Allolio B: New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line. Eur J Clin Invest 2000; 30(suppl 3):76-82 (Pubitemid 32154555)
155. Atucha E, Hammerschmidt F, Zolle I, Sieghart W, Berger ML: Structure-activity relationship of etomidate derivatives at the GABA(A) receptor: Comparison with binding to 11beta-hydroxylase. Bioorg Med Chem Lett 2009; 19:4284-7
156. Cotten JF, Husain SS, Forman SA, Miller KW, Kelly EW, Nguyen HH, Raines DE: Methoxycarbonyl-etomidate: A novel rapidly metabolized and ultra-short-acting etomidate analogue that does not produce prolonged adrenocortical suppression. ANESTHESIOLOGY 2009; 111:240-9
157. Cotten JF, Forman SA, Laha JK, Cuny GD, Husain SS, Miller KW, Nguyen HH, Kelly EW, Stewart D, Liu A, Raines DE: Carboetomidate: A pyrrole analog of etomidate designed not to suppress adrenocortical function. ANESTHESIOLOGY 2010; 112:637-44
158. Glen JB: Animal studies of the anaesthetic activity of ICI 35 868. Br J Anaesth 1980; 52:731-42
159. Marietta MP, Way WL, Castagnoli N Jr, Trevor AJ: On the pharmacology of the ketamine enantiomorphs in the rat. J Pharmacol Exp Ther 1977; 202:157-65 (Pubitemid 8151934)
160. Christensen HD, Lee IS: Anesthetic potency and acute toxicity of optically active disubstituted barbituric acids. Toxicol Appl Pharmacol 1973; 26:495-503