Pharmacological Intervention at Ionotropic Glutamate Receptor Complexes

Authors: Planells-Cases, Rosa; Lerma, Juan; Ferrer-Montiel, Antonio

Source: Current Drug Metabolism, Volume 12, Number 28, October 2006 , pp. 3583-3596(14)

Publisher: Bentham Science Publishers

Buy & download fulltext article:

Price: $63.10 plus tax (Refund Policy)

Abstract:

L-glutamate is considered the main excitatory neurotransmitter in the mammalian brain. Paradoxically, Lglutamate is also the most important excitotoxin pivotally involved in the aetiology of several neurodegenerative diseases such as stroke, Alzheimer, Parkinson, amyotropic lateral sclerosis, Huntington and neuropathic pain. L-glutamate signalling is transduced both presynaptically and postsynaptically by metabotropic and ionotropic receptors. Three types of glutamate-gated channels integrate the synaptic signal, namely AMPA, kainate and NMDA receptors. Sustained activation of these receptors, and especially of the NMDA receptor, is a casuistic phenomenon that leads to the neuronal death underlying neurodegeneration. Thus, pharmacological intervention at these neuronal receptors and their synaptic protein complexes is a valuable therapeutic strategy. The approval of memantine, a safe, well-tolerated uncompetitive NMDA antagonist for the treatment of moderate to severe Alzheimer dementia validates ionotropic glutamate receptors as key therapeutic targets of neurodegenerative diseases in humans. As a consequence, an enormous effort is being carried out to identify and develop safe and potent antagonists for the clinics. In this review, we will describe progress in this important arena of human health.

Keywords: AMPA receptor; YM872; Kainate receptors; NR2A subunits; NMDA antagonist; neurodegeneration

Document Type: Research article

Affiliations: 1: Instituto Biologia Molecular y Celular, Ed. Torregaitan, Universidad Miguel Hernandez, Av. De la Universidad s/n, 03202 Elche, Alicante, Spain.

Publication date: 2006-10-01

More about this publication?

Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

Pharmacological Intervention at Ionotropic Glutamate Receptor Complexes

Buy & download fulltext article:

Tools

Key

Text size:

Useful pages