The Ability of New Non-Competitive Glutamate Receptor Blockers to Weaken Motor Disorders in Animals


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Abstract

The ability of mono- and dicationic phenylcyclohexyl derivatives, which are non-competitive glutamate antagonists, to prevent convulsions induced in mice by intragastric NMDA or kainate, to weaken catalepsy induced in rats by haloperidol, and to exert their own influences of movement activity and behavior in animals was studied. The actions of study compounds were compared with those of the known NMDA antagonists memantine and dizocilpine. NMDA-induced convulsions were effectively prevented by both mono- and dications, while only dications were effective against kainate convulsions. Anticataleptic activity was significantly more marked in monocations, which lacked the ability to block non-NMDA receptors. Side effects on motor coordination were less marked with study compounds than with dizocilpine. Thus, the effects of phenylcyclohexyl derivatives in in vivo experimental models correlate with their anti-NMDA and anti-AMPA activity. They can be regarded as potential agents for treating parkinsonism and other motor disorders.

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