Interaction of steroids with the GABA(A) receptor.
Over the last two decades there has been a resurgence of interest in steroids as potential therapeutics for central nervous system disorders. This interest followed the discovery that neurosteroids and neuroactive steroids are potent modulators of GABA(A) receptor function. This article traces those developments focussing particularly on the structure-activity relationships that have been identified through synthetic modification of established ligands, but also examines the influence of GABA(A) receptor subunit composition for steroid modulation. The review then covers some of the physiological effects such steroids are liable to exert and their therapeutic potential for treating central nervous system disorders including epilepsy, anxiety and insomnia.
Hamilton
Niall M
NM
Department of Medicinal Chemistry, Organon Laboratories Ltd., Newhouse, ML1 5SH, Scotland, UK. n.hamilton@organon.nhe.akzonobel.nl
D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy; D018757:GABA Modulators / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013237:Stereoisomerism; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D018757:GABA Modulators; D021122:Protein Subunits; D011963:Receptors, GABA-A; D013256:Steroids