GABA A receptors

Neurosteroids are neuroactive steroids, which are synthesized in the brain. Neurosteroids can bind to and modulate the activity of y-aminobuty tie acidA(GABA A) receptors. 

Chester JA, Cunningham CL GABA(A) receptor modulation of the rewarding and aversive effects of ethanol. Alcohol 26 131—143, 2002 Chick J Safety issues concerning the use of disulfiram in treating alcohol dependence. Drug Saf 20 427 35, 1999... 

Edenberg HJ, Dick DM, Xuei X, et al Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet 74 705-714, 2004... 

Atack JR Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. Curr Drug Target CNS Neurol Disord 2 213—232, 2003... 

Gamma aminobutyric acid (GABA) receptors are located on the postsynaptic membranes of inhibitory synapses of both vertebrates and insects and contain within their membrane-spanning structure a chloride ion channel. They are found in both vertebrate brains and invertebrate cerebral ganglia (sometimes referred to as brains) as well as in insect muscles. Particular attention has been given to one form of this receptor—the GABA-A receptor—as a target for novel insecticides (Eldefrawi and Eldefrawi 1990). It is found both in insect muscle and vertebrate brain. The remainder of this description will be restricted to this form. 

Schofield, PR, Darlison, MG, Fujita, N, Burt, DR, Stephenson, FA, Rodriguez, H, Rhee, LM, Ramachandran, J, Reale, V, Glencorse, TA et al. (1987) Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family. Nature 328 221-227. 

Consider propofol pharmacotherapy, as it agonizes GABA-A receptors and antagonizes NMDA receptors. Phenobarbital can be used as an alternative... 

Kaur, S., Panchal, M., Faisal, M. et al. (2004). Long term blocking of GABA-A receptor in locus coeruleus by bilateral microinfusion of picrotoxin reduced rapid eye movement sleep and increased brain Na-K ATPase activity in freely moving normally behaving rats. Behav. Brain Res. 151, 185-90. 

Baumann, S. W., Baur, R. 8r Sigel, E. (2003). Individual properties of the two functional agonist sites in GABA(A) receptors./. Neurosci. 23, 11158-66. 

GABA, and molecules that act at GABA-A receptors, have been classically recognized as hypnotics (i.e. benzodiazepines) and anesthetics (i.e. barbiturates). Benzodiazepine (BZD) receptors, a modulatory site on the GABA-A receptor, were... 

Johnston G. A. (2005). GABA(A) receptor channel pharmacology. Curr. Pharm. Des. 11, 1867-85. 

Molher H., Malherbe P., Draguhn A. et al. (1990). GABA-A-receptor subunits ... 

Hood HM, Buck KJ. Allelic variation in the GABA-A receptor yl subunit is associated with genetic susceptibility to ethanol-induced motor incoordination and hypothermia, conditioned taste aversion, and withdrawal in BxD/Ty recombinant inbred mice. Alcohol Clin Exp Res 2000 24 1327-1334. 

Baraldi M Supersensitivity of GABA-A receptors in hepatic encephalopathy. Neurochem Res 1990 15 153-160. 

Basile AS, Gammal SH, Jones EA, Skolnick P GABA-A receptor complex in an experimental model of hepatic encephalopathy Evidence for elevated levels of an endogenous benzodiazepine receptor complex ligand. J Neurochem 1989 53 1057-1063. 

The epilepsies constitute a common, serious neurological disorder in humans, affecting approximately 60 million people worldwide. Well in excess of 40 distinct epileptic syndromes have been identified to date. Current treatment is only symptomatic except in uncommon instances when surgical treatment is possible. While available antiseizure medications target ion channels such as the y-amino-butyric acid (GABA)a receptor and voltage activated sodium (Na+) channels, current research seeks to elucidate the cellular and molecular mechanisms by which a normal brain becomes epileptic. Hopefully, this research will lead to the identification of new targets for which small molecules can be identified and used for prevention or cure of epilepsy. 

---