Professor and Head
Anesthesiology
Internal Medicine
Email Website Contact Info More Publications
The major focus of my laboratory is elucidation of the molecular mechanism(s) through which anesthetics act to depress nervous system function. We are specifically interested in identifying the target molecules with which anesthetics interact, and in characterizing these interactions. Two general methods are used in the laboratory to observe the low affinity binding interactions of anesthetics with specific proteins (not observable using conventional binding methodology). 19F-NMR (nuclear magnetic resonance) exchange-spectroscopic methods are used to characterize the kinetics of fluorinated volatile anesthetic binding to purified proteins. To identify the specific nervous system proteins with which anesthetics interact, we have developed photo-labile anesthetic molecules and undertaken photoaffinity labeling studies. Photolabeling studies with fluorinated volatile anesthetics have identified several proteins that contain specific binding sites for the fluorinated volatile anesthetics. More recently, we have developed an anesthetic steroid that can act as a photolabeling reagent. This reagent should allow us to identify the specific CNS proteins that bind anesthetic steroids and to begin a molecular characterization of these sites. The long-term goals of the lab are to synthesize photolabeling reagents for several classes of anesthetics and to use these agents to classify and characterize the binding sites responsible for producing anesthesia.
Research Publications
Mennerick S, Zeng CM, Benz A, Shen W, Izumi Y, Evers AS, Covey DF, Zorumski CF. Effects on gamma-Aminobutyric Acid (GABA)(A) Receptors of a Neuroactive Steroid That Negatively Modulates Glutamate Neurotransmission and Augments GABA eurotransmission. Mol Pharmacol. 2001 Oct;60(4):732-41.
Covey DF, Han M, Kumar AS, de La Cruz MA, Meadows ES, Hu Y, Tonnies A, Nathan D, Coleman M, Benz A, Evers AS, Zorumski CF, Mennerick S. Neurosteroid analogues. 8. Structure-activity studies of N-acylated 17a-aza-D-homosteroid analogues of the anesthetic steroids (3alpha, 5alpha)- and (3alpha,5beta)-3-hydroxypregnan-20-one. J Med Chem. 2000 Aug 24;43(17):3201-4.
Paradiso K, Sabey K, Evers AS, Zorumski CF, Covey DF, Steinbach JH. Steroid inhibition of rat neuronal nicotinic alpha4beta2 receptors expressed in HEK 293 cells. Mol Pharmacol. 2000 Aug;58(2):341-51.
Covey DF, Nathan D, Kalkbrenner M, Nilsson KR, Hu Y, Zorumski CF, Evers AS. Enantioivity of pregnanolone-induced gamma-aminobutyric acid(A) receptor modulation and anesthesia. J Pharmacol Exp Ther. 2000 Jun;293(3):1009-16.
Evers AS, Steinbach JH. Double-edged swords: volatile anesthetics both enhance and inhibit ligand-gated ion channels. Anesthesiology. 1999 Jan;90(1):1-3.
Contact Info
Alex Evers, M.D.
Office Phone: 314-454-8702
Lab Phone: 314-362-8557
Campus Box: 8054
Fax: 314-454-5572
eversa@wustl.edu
http://elysium.wustl.edu/aelab/
