ABSTRACT
Amongst ionotropic glutamatergic receptors, the AMPA receptor subtype has been recognized as a major contributor to the fast excitatory neurotransmission in the central nervous system and the expression and maintenance of longterm potentiation. This receptor subtype also represents an interesting target to develop innovative therapeutic drugs such as positive allosteric modulators (AMPA receptor potentiators) since the enhancement of AMPA signals is expected to be beneficial in the management of several neurological disorders such as depression, schizophrenia, Parkinson's disease and learning-memory deficits linked to Alzheimer's disease. This article is dedicated to the use of (hetero) aromatic ring-fused thiadiazines (i.e. benzo- pyrido- and thienothiadiazines) as core structures for the discovery of new positive allosteric modulators of AMPA receptors. Recent advances exploring other chemotypes in the field of AMPA potentiators is the object of a separate review of the present issue.
Subject(s)
Receptors, AMPA/chemistry , Thiadiazines/chemistry , Allosteric Regulation , Humans , Nervous System Diseases/drug therapy , Receptors, AMPA/metabolism , Thiadiazines/therapeutic useABSTRACT
First described by Alois Alzheimer in 1907, Alzheimer's disease (AD) is the most common dementia type, affecting approximately 20 million people worldwide. As the population is getting older, AD is a growing health problem. AD is currently treated by symptomatic drugs, the acetylcholinesterase inhibitors, based on the cholinergic hypothesis (1976). During the past decade, advances in neurobiology have conducted to the identification of new targets. Although some of these innovative approaches tend to delay onset of AD, others are still symptomatic. In this review, we present an overview of the several strategies and new classes of compounds against AD.
