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

Ward, Simon E., Harries, Mark H., Aldegheri, Laura, Bradford, Andrea M., Ballini, Elisa, Dawson, Lee, Lacroix, Laurent, Pardoe, Joanne, Starr, Kathryn, Weil, Annette, Waters, Kerry, Atack, John R. and Woolley, Marie 2020. Pharmacological characterisation of MDI-222, a novel AMPA receptor positive allosteric modulator with an improved safety profile. Journal of Psychopharmacology 34 (1) , pp. 93-102. 10.1177/0269881119872198

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Biosciences
Publisher:	SAGE
ISSN:	0269-8811
Date of First Compliant Deposit:	2 January 2020
Date of Acceptance:	28 July 2019
Last Modified:	13 Nov 2020 10:45
URI:	http://orca.cf.ac.uk/id/eprint/128151

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