Non-competitive AMPA Antagonists of 2,3-Benzodiazepine Type

Title: Non-competitive AMPA Antagonists of 2,3-Benzodiazepine Type

Volume: 8 Issue: 10

Author(s): Sandor Solyom and Istvan Tarnawa

Affiliation:

Keywords: non-competitive ampa antagonists, benzodiazepine type, ampa receptors, 2,3-benzodiazepines, phthalazines, antiepileptic drugs

Abstract: The discovery of the selective AMPA antagonist character of 2,3-benzodiazepine derivative GYKI 52466 (5) in the late eighties and the recognition of the non-competitive nature of its mode of action some years later set off the world-wide search for novel class of drugs. Notably the quest to develop new antiepileptic and neuroprotective medicines, which allosterically inhibit the AMPA sensitive glutamate operated channels. This review summarises our present knowledge about the allosteric site, dubbed “GYKI site” where the 2,3-benzodiazepines are supposed to bind to. The structure-activity relationships among AMPA antagonist 2,3-benzodiazepines and their structural analogues with similar biological profile are reviewed in a possibly comprehensive fashion. The chemical synthesis of 2,3-benzodiazepines is shortly described. The in vitro and in vivo experimental methods used for pharmacological characterisation of the biologically active compounds are briefly explained. Finally the therapeutic potential of 2,3-benzodiazepines i.e. the main fields of their clinical utility are outlined with special regard to talampanel (20) in the light of the ongoing clinical trials with this new drug candidate.

Cite this article as:

Solyom Sandor and Tarnawa Istvan, Non-competitive AMPA Antagonists of 2,3-Benzodiazepine Type, Current Pharmaceutical Design 2002; 8 (10) . https://dx.doi.org/10.2174/1381612024607081