Stuart Forman

Summary

Affiliation: Massachusetts General Hospital
Country: USA

Publications

  1. ncbi request reprint 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
    S Shaukat Husain
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Med Chem 46:1257-65. 2003
  2. pmc State-Dependent Etomidate Occupancy of Its Allosteric Agonist Sites Measured in a Cysteine-Substituted GABAA Receptor
    Deirdre S Stewart
    Department of Anesthesia Critical Care and Pain Medicine, Jackson 444, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114
    Mol Pharmacol 83:1200-8. 2013
  3. pmc Monod-Wyman-Changeux allosteric mechanisms of action and the pharmacology of etomidate
    Stuart A Forman
    Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
    Curr Opin Anaesthesiol 25:411-8. 2012
  4. pmc Tryptophan mutations at azi-etomidate photo-incorporation sites on alpha1 or beta2 subunits enhance GABAA receptor gating and reduce etomidate modulation
    Deirdre Stewart
    Beecher Mallincrodt Labs, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Mol Pharmacol 74:1687-95. 2008
  5. ncbi request reprint Photoactivated 3-azioctanol irreversibly desensitizes muscle nicotinic ACh receptors via interactions at alphaE262
    Stuart A Forman
    Department of Anesthesia and Critical Care, Jackson 4, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Biochemistry 46:11911-8. 2007
  6. pmc Molecular approaches to improving general anesthetics
    Stuart A Forman
    Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Jackson 4, MGH, 55 Fruit Street, Boston, MA 02114, USA
    Anesthesiol Clin 28:761-71. 2010
  7. pmc Anesthetic sites and allosteric mechanisms of action on Cys-loop ligand-gated ion channels
    Stuart A Forman
    Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Jackson 444, Boston, MA 02114, USA
    Can J Anaesth 58:191-205. 2011
  8. pmc General anesthetics and molecular mechanisms of unconsciousness
    Stuart A Forman
    Department of Anaesthesia, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Int Anesthesiol Clin 46:43-53. 2008
  9. pmc Mutations in the GABAA receptor that mimic the allosteric ligand etomidate
    Stuart A Forman
    Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
    Methods Mol Biol 796:317-33. 2012
  10. pmc Clinical and molecular pharmacology of etomidate
    Stuart A Forman
    Harvard Medical School, Boston, Massachusetts, USA
    Anesthesiology 114:695-707. 2011

Collaborators

Detail Information

Publications30

  1. ncbi request reprint 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
    S Shaukat Husain
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Med Chem 46:1257-65. 2003
    ..The latter increase was confined to a proteolytic fragment containing the first three transmembrane segments. Thus, R-(+)-azietomidate is a potent stereoselective general anesthetic and an effective photolabel...
  2. pmc State-Dependent Etomidate Occupancy of Its Allosteric Agonist Sites Measured in a Cysteine-Substituted GABAA Receptor
    Deirdre S Stewart
    Department of Anesthesia Critical Care and Pain Medicine, Jackson 444, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114
    Mol Pharmacol 83:1200-8. 2013
    ..Our results support MWC models as valid frameworks for understanding the agonism, coagonism, and modulation of ligand-gated ion channels...
  3. pmc Monod-Wyman-Changeux allosteric mechanisms of action and the pharmacology of etomidate
    Stuart A Forman
    Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
    Curr Opin Anaesthesiol 25:411-8. 2012
    ..However, the mathematical formalism of these mechanisms makes them difficult to comprehend...
  4. pmc Tryptophan mutations at azi-etomidate photo-incorporation sites on alpha1 or beta2 subunits enhance GABAA receptor gating and reduce etomidate modulation
    Deirdre Stewart
    Beecher Mallincrodt Labs, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Mol Pharmacol 74:1687-95. 2008
    ..Furthermore, quantitative mechanistic analysis demonstrated that wild-type and mutant results are consistent with the presence of only one class of etomidate sites mediating both agonist potentiation and direct activation...
  5. ncbi request reprint Photoactivated 3-azioctanol irreversibly desensitizes muscle nicotinic ACh receptors via interactions at alphaE262
    Stuart A Forman
    Department of Anesthesia and Critical Care, Jackson 4, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Biochemistry 46:11911-8. 2007
    ..Occupation of this pocket by hydrophobic molecules stabilizes a desensitized state by slowing resensitization...
  6. pmc Molecular approaches to improving general anesthetics
    Stuart A Forman
    Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Jackson 4, MGH, 55 Fruit Street, Boston, MA 02114, USA
    Anesthesiol Clin 28:761-71. 2010
    ..The goal of this review is to highlight these important developments and describe translational research on new general anesthetics with the potential to improve and reshape clinical care...
  7. pmc Anesthetic sites and allosteric mechanisms of action on Cys-loop ligand-gated ion channels
    Stuart A Forman
    Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Jackson 444, Boston, MA 02114, USA
    Can J Anaesth 58:191-205. 2011
    ....
  8. pmc General anesthetics and molecular mechanisms of unconsciousness
    Stuart A Forman
    Department of Anaesthesia, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Int Anesthesiol Clin 46:43-53. 2008
  9. pmc Mutations in the GABAA receptor that mimic the allosteric ligand etomidate
    Stuart A Forman
    Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
    Methods Mol Biol 796:317-33. 2012
    ..Furthermore, these mutations reduce receptor modulation by etomidate. Both of these observations support the hypothesis that these methionine residues form part of the etomidate binding pocket...
  10. pmc Clinical and molecular pharmacology of etomidate
    Stuart A Forman
    Harvard Medical School, Boston, Massachusetts, USA
    Anesthesiology 114:695-707. 2011
    ..Based on this deepening understanding of molecular targets and actions, new etomidate derivatives are being investigated as potentially improved sedative-hypnotics or for use as highly selective inhibitors of adrenal steroid synthesis...
  11. pmc p-Trifluoromethyldiazirinyl-etomidate: a potent photoreactive general anesthetic derivative of etomidate that is selective for ligand-gated cationic ion channels
    S Shaukat Husain
    Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 32 Fruit Street, Boston, Massachusetts 02114, USA
    J Med Chem 53:6432-44. 2010
    ..TFD-etomidate's novel pharmacology is unlike that of etomidate derivatives with photoactivable groups in the ester position, which behave like etomidate, suggesting that it will further enhance our understanding of anesthetic mechanisms...
  12. ncbi request reprint Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels
    S Shaukat Husain
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114 USA
    J Med Chem 49:4818-25. 2006
    ..Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia...
  13. pmc Gamma-amino butyric acid type A receptor mutations at beta2N265 alter etomidate efficacy while preserving basal and agonist-dependent activity
    Rooma Desai
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA, USA
    Anesthesiology 111:774-84. 2009
    ..Mutations at beta residue 265 (Ser in beta1; Asn in beta2 or beta3) profoundly affect etomidate sensitivity. Whether these mutations alter etomidate binding remains uncertain...
  14. ncbi request reprint Classic benzodiazepines modulate the open-close equilibrium in alpha1beta2gamma2L gamma-aminobutyric acid type A receptors
    Dirk Rüsch
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA
    Anesthesiology 102:783-92. 2005
    ..The authors tested the hypothesis that benzodiazepine site ligands modulate alpha1beta2gamma2L GABAA receptor gating both in the absence of orthosteric agonists and when the orthosteric sites are occupied...
  15. pmc Time-resolved photolabeling of the nicotinic acetylcholine receptor by [3H]azietomidate, an open-state inhibitor
    David C Chiara
    Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
    Mol Pharmacol 75:1084-95. 2009
    ....
  16. ncbi request reprint Gating allosterism at a single class of etomidate sites on alpha1beta2gamma2L GABA A receptors accounts for both direct activation and agonist modulation
    Dirk Rüsch
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA
    J Biol Chem 279:20982-92. 2004
    ..This model also correctly predicts the actions of etomidate on GABA(A) receptors containing a point mutation that increases constitutive gating activity...
  17. pmc Photo-activated azi-etomidate, a general anesthetic photolabel, irreversibly enhances gating and desensitization of gamma-aminobutyric acid type A receptors
    Huijun Zhong
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Anesthesiology 108:103-12. 2008
    ..The authors examine the irreversible effects of azi-etomidate photo-modification on functional GABA(A) receptors in cell membranes...
  18. ncbi request reprint Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: the effects on agonist enhancement, direct activation, and inhibition
    Douglas E Raines
    Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA
    Anesth Analg 96:112-8, table of contents. 2003
    ....
  19. ncbi request reprint Nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes inhibit alpha(4)beta(2) neuronal nicotinic acetylcholine receptors
    Douglas E Raines
    Department of Anesthesia, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114, USA
    Anesth Analg 95:573-7, table of contents. 2002
    ..However, the inhibition of neuronal nicotinic acetylcholine receptors may account for the amnestic activities of general anesthetics and nonimmobilizers...
  20. ncbi request reprint Gating-enhanced accessibility of hydrophobic sites within the transmembrane region of the nicotinic acetylcholine receptor's {delta}-subunit. A time-resolved photolabeling study
    Enrique Arevalo
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Biol Chem 280:13631-40. 2005
    ..Contact with these residues occurs on the time scale of a rapid phase of TID inhibition in Torpedo nAChRs, suggesting the formation of a transient hydrophobic pocket between M1, M2, and M3 in the delta-subunit during gating...
  21. ncbi request reprint Mechanisms of general anesthesia: from molecules to mind
    George A Mashour
    Harvard Medical School, and Massachusetts General Hospital, Boston, MA 02114, USA
    Best Pract Res Clin Anaesthesiol 19:349-64. 2005
    ..We also present a framework to aid in thinking about the actions of these agents, highlighting the relationship between putative targets at the molecular level and the more integrated functional changes in behavior and consciousness...
  22. pmc Carboetomidate: a pyrrole analog of etomidate designed not to suppress adrenocortical function
    Joseph F Cotten
    Harvard Medical School, Boston, Massachusetts, USA
    Anesthesiology 112:637-44. 2010
    ....
  23. pmc Methoxycarbonyl-etomidate: a novel rapidly metabolized and ultra-short-acting etomidate analogue that does not produce prolonged adrenocortical suppression
    Joseph F Cotten
    Harvard Medical School, Boston, Massachusetts, USA
    Anesthesiology 111:240-9. 2009
    ....
  24. ncbi request reprint Differential effects of serotonin and dopamine on human 5-HT3A receptor kinetics: interpretation within an allosteric kinetic model
    Ken Solt
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Neurosci 27:13151-60. 2007
    ....
  25. ncbi request reprint Correlating the clinical actions and molecular mechanisms of general anesthetics
    Ken Solt
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA
    Curr Opin Anaesthesiol 20:300-6. 2007
    ..To summarize recent in-vitro and in-vivo research on molecular mechanisms of general anesthetics' actions...
  26. ncbi request reprint Mechanisms of actions of inhaled anesthetics
    Jason A Campagna
    Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA
    N Engl J Med 348:2110-24. 2003
  27. pmc A novel missense mutation in SLC34A3 that causes hereditary hypophosphatemic rickets with hypercalciuria in humans identifies threonine 137 as an important determinant of sodium-phosphate cotransport in NaPi-IIc
    Graciana Jaureguiberry
    Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
    Am J Physiol Renal Physiol 295:F371-9. 2008
    ..M137 thus may uncouple sodium-phosphate cotransport, suggesting that this amino acid residue has an important functional role in human NaPi-IIc...
  28. ncbi request reprint Coupled and uncoupled gating and desensitization effects by pore domain mutations in GABA(A) receptors
    Michaela Scheller
    Klinik fuer Anaesthesiologie der Technischen Universitaet Muenchen, Klinikum rechts der Isar, D 81675 Munich, Germany
    J Neurosci 22:8411-21. 2002
    ..The effects of the alpha1(L264T) mutation suggest that the conserved leucines may play a role in gating-desensitization coupling...
  29. ncbi request reprint Of mice and nematodes
    Stuart A Forman
    Anesthesiology 105:442-4. 2006
  30. pmc Protein kinase C modulates inactivation of Kv3.3 channels
    Rooma Desai
    Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 283:22283-94. 2008
    ....

Research Grants8

  1. Volatile Anesthesia and the GABAA Receptor Gamma Subunit
    Stuart Forman; Fiscal Year: 2007
    ..abstract_text> ..
  2. Volatile Anesthesia and the GABAA Receptor Gamma Subunit
    Stuart Forman; Fiscal Year: 2009
    ..abstract_text> ..
  3. General Anesthetic Sites in GABA-A Receptor Subunit Interfacial Pockets
    Stuart A Forman; Fiscal Year: 2010
    ....