TY - JOUR
T1 - Mechanisms of neurosteroid interactions with GABAA receptors
AU - Akk, Gustav
AU - Covey, Douglas F.
AU - Evers, Alex S.
AU - Steinbach, Joe Henry
AU - Zorumski, Charles F.
AU - Mennerick, Steven
N1 - Funding Information:
This work was supported by National Institutes of Health grants GM47969 (J.H.S., C.F.Z., D.F.C.), AA14707 (G.A.), AA12951 (C.F.Z.), AA12952, NS54174, and MH78823 (S.M.) and by grants from the American Health Assistance Foundation (S.M.) and the Bantly Foundation (C.F.Z.). J.H.S. is the Russell and Mary Shelden Professor of Anesthesiology. We thank the colleagues from our program who have participated in the studies cited herein.
PY - 2007/10
Y1 - 2007/10
N2 - Neuroactive steroids have some of their most potent actions by augmenting the function of GABAA receptors. Endogenous steroid actions on GABAA receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABAA receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.
AB - Neuroactive steroids have some of their most potent actions by augmenting the function of GABAA receptors. Endogenous steroid actions on GABAA receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABAA receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.
KW - Anesthesia
KW - Electrophysiology
KW - Enantiomer
KW - GABA
KW - Neurosteroid
KW - Photoaffinity label
UR - http://www.scopus.com/inward/record.url?scp=34548558868&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2007.03.004
DO - 10.1016/j.pharmthera.2007.03.004
M3 - Review article
C2 - 17524487
AN - SCOPUS:34548558868
SN - 0163-7258
VL - 116
SP - 35
EP - 57
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 1
ER -