Current Topics in Medicinal Chemistry - Volume 2, Issue 8, 2002

GABA-A receptors are the major inhibitory neurotransmitter receptors in the brain and are the site of action of many clinically important drugs. These receptors are composed of five subunits that can belong to eight different subunit classes. Depending on their subunit composition, these receptors exhibit distinct pharmacological and electrophysiological properties. Recent studies on recombinant and native GABA-A recept Read More

The GABA-A receptor system is implicated in a number of neurological diseases, making GABA-A receptor ligands interesting as potential therapeutic agents. Only a few different classes of structures are currently known as ligands for the GABA recognition site on the GABA-A receptor complex, reflecting the very strict structural requirements for GABA-A receptor recognition and activation. Within the series of compoun Read More

Ligands of the benzodiazepine binding site of the GABA-A receptor come in three flavors: positive allosteric modulators, negative allosteric modulators and antagonists, all of which can bind with high affinity. The GABA-A receptor is a pentameric protein which forms a chloride selective ion channel and ligands of the benzodiazepine binding site stabilize three different conformations of this receptor channel. Classical benz Read More

Considerable evidence has been provided these last years for the involvement of the GABA-A receptor complex in memory processes. Compounds that enhance the action of GABA, such as benzodiazepines, impair memory processing. On the contrary, compounds that reduce the action of GABA, such as ß-CCM, pentylenetetrazol or picrotoxin, have the opposite action, that is : enhance memory processing. All these actions Read More

This review describes the new research developments that have established the CNS-activity of some natural flavonoids. The properties of flavone, chrysin, apigenin and cirsiliol are described and a survey of the occurrence of ligands for the benzodiazepine binding site in the flavonoid field is attempted. Natural compounds, structurally related to flavonoids and with similar CNS-activities, are also included.A medicinal chemistry Read More

Despite the fact that ethanol is one of the most widely used psychoactive agents, the mechanisms and sites of action by which it modifies brain functions are only now being elucidated. Studies over the last decade have shown that ethanol can specifically alter the function of several ligand-activated ion channels including Nmethyl- D-aspartate (NMDA), serotonin (5-HT3), glycine and GABA-A receptors. After several years of Read More

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 modificatio Read More

GABA-C receptors belong to the nicotinicoid superfamily of ionotropic receptors that include nicotinic acetylcholine receptors, bicuculline-sensitive GABA-A receptors, strychnine-sensitive glycine receptors and 5HT3 serotonin receptors. The GABA-C receptor concept arose from medicinal chemical studies of a conformationally restricted analog of GABA. Receptors matching the predicted properties of GABA-C receptors we Read More