The quest for treatment of cognitive impairment: AMPA and mGlu5 receptor modulators

Abstract

Background: Modulation of synaptic functions holds great potential as therapeutic strategies to manage neurodegenerative disorders in which cognitive functions are usually impaired as a core symptom of the disorders. The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) and subtype 5 metabotropic glutamate receptors (mGluR5s) are critically involved in a variety of cognitive functions and deficits and their selective modulators may be developed into effective drugs for enhancing cognition and reducing cognitive deficits. Objective: This short review covers recent advances in research development of AMPAR and mGluR5 modulators as potential therapeutics for the treatment of cognitive impairment. Results/conclusion: Selective modulators of AMPARs and mGluR5s possess several advantages over the receptor agonists/antagonists as potential novel therapeutics for cognitive impairment. Positive allosteric modulators have potential therapeutic value in correcting the glutamatergic hypofunction associated with some cognitive disorders without inducing neuronal excitotoxicity. Their negative modulators, on the other hand, reduce excessive glutamatergic activity without shutting down the neural circuits as the AMPAR antagonists do. Further studies are, however, needed, particularly those with in vivo utility evaluation.