Recent advances in the pharmacology of quaternary salts of bicuculline.

Abstract

GABA is the major inhibitory transmitter in the mammalian adult CNS where it acts mainly on GABAA and GABAB receptors. GABAA receptors are heteromultimeric complexes comprising probably five subunits that form a Cl−-permeable channel. These subunits belong to α, β, γ, δ and ϵ families and co-assemble with a variable stoichiometry 1 Sieghart W. Pharmacol. Rev. 1995; 47: 181-234 PubMed Google Scholar , 2 McKernan R.H. Whiting P.J. Trends Neurosci. 1996; 19: 139-143 Abstract Full Text PDF PubMed Scopus (1073) Google Scholar . In addition to the site where GABA binds, most of these receptors also contain binding sites for benzodiazepines and neurosteroids, as well as alcohol and volatile anaesthetics 3 Macdonald R.L. Olsen R.W. Annu. Rev. Neurosci. 1994; 17: 569-602 Crossref PubMed Scopus (1781) Google Scholar , 4 Franks N.P. Lieb W.R. Nature. 1994; 367: 607-614 Crossref PubMed Scopus (1625) Google Scholar , 5 Mihic S.J. et al. Nature. 1997; 389: 385-389 Crossref PubMed Scopus (1096) Google Scholar . Activation of GABAA receptors leads to fast inhibitory postsynaptic potentials (IPSPs) in most brain areas. Because they are often located close to the site where action potentials are generated, these receptors constitute a very strong inhibitory system.