2,3-Benzodiazepine compounds are an important family
of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
(AMPAR) antagonists that act in a noncompetitive manner. Due to
the critical role of AMPARs in the synapse and various neurological
diseases, significant scientific interest in elucidating the molecular basis
of the function of the receptors has spiked. The analogues were
synthesized to assess the functional consequence of removing the amine
group of the phenyl ring, the potency and efficacy of inhibition by
substituting a halogen group at the meta vs ortho position of the phenyl
ring, and layout the prediction of potential drug candidates for AMPAR
hyperactivation. Using the whole-cell patch-clamp technique, we
assessed the effect of the derivative on the amplitude of various
AMPA-type glutamate receptors and calculated the desensitization and
deactivation rates before and after treatment of HEK293 cells. We noticed that the amino group is not necessary for inhibition as
long as an electron-withdrawing group is placed on the meta position of the phenyl ring of BDZ. Furthermore, compound 4a
significantly inhibited and affected the desensitization rate of the tested AMPARs but showed no effect on the deactivation rate. The
current study paves the way to a better understanding of AMPARs and provides possible drug candidates of 2,3-BDZ different from
the conventional derivatives.

Title

ACS Omega

Publisher

American Chemical Society

Publisher Country

United States of America

Indexing

Thomson Reuters

Impact Factor

2.584

Publication Type

Both (Printed and Online)

Volume

5

Year

2020

Pages

3588–3595