Pharmacological characterisation of MDI-222, a novel AMPA receptor positive allosteric modulator with an improved safety profile.

ABSTRACT:

Purpose

There is considerable interest in positive allosteric modulators (PAMs) of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) subtype of ionotropic glutamate receptors as therapeutic agents for a range of cognitive and mood disorders. However, the challenge is to increase AMPA receptor (AMPAR) function sufficient to enhance cognitive function but not to the extent that there are mechanism-related pro-convulsant or convulsant side effects. In this present study, we report the preclinical pharmacology data for MDI-222, an AMPAR PAM which enhances cognition but has a much reduced side-effect (i.e. convulsant) liability relative to other molecules of this mechanism.

Methods

The pharmacological effects of MDI-222 were characterised in in vitro and in vivo precl

SUBMITTER: Ward SE 

PROVIDER: S-EPMC7610887 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature