2,3-Benzodiazepine AMPA Antagonists

Article type: Research Article

Authors: Tarnawa, István | Vize, E. Sylvester

Affiliations: CHINOIN Pharmaceutical Works Co. Ltd., To u. 1-5, H-1045 Budapest, Hungary | Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083 Budapest, Hungary

Note: [] Corresponding author: I. Tarnawa, P.O. Box 110, H-1325 Budapest, Hungary. Tel.: + 36 1 36909000-2603; Fax: + 36 1 3705412; E-mail: h13767tar@ella.hu

Abstract: The 2,3-benzodiazepine GYKI 52466 (1-(4-aminophenyl)-4 methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine) and its analogues represent a family of selective AMPA antagonists. They modulate AMPA channel functions through an allosteric site on the receptor, which is probably different from the ones involved in the actions of cyclothiazide and aniracetam. These compounds are frequently used as research tools to elucidate glutamate receptor-mediated functions. The most effective members of the family inhibit AMPA-induced currents in the submicromolar range. In addition, they are active at low systemic doses in various in vivo experimental models and also possess a good oral bioavailability. In vitro and in vivo pharmacological results with 2,3-benzodiazepine AMPA antagonists indicate their potential therapeutical value in treating a great variety of central nervous system diseases, of which epilepsy and neurodegenerative disorders are regarded as the most important.

Keywords: GYKI 52466, epilepsy, spasticity, pain disorders, neuroprotection, neurodegenerative disorders

Journal: Restorative Neurology and Neuroscience, vol. 13, no. 1-2, pp. 41-57, 1998