The acute antiparkinsonian and antidyskinetic effect of @entity42863 , a novel metabotropic @entity2227 receptor type 5 antagonist, in L-Dopa-treated XXXX monkeys.

@entity5212 @entity2227 @entity5434 @entity42863 @entity910 @entity10092 @entity191
Overactivity of glutamatergic transmission has been implicated in @entity191 ( @entity191 ) and levodopa (L-Dopa)-induced @entity910 . Striatal metabotropic @entity2227 receptors type 5 ( @entity10092 ) are abundant and provide specific targets to modulate glutamatergic activity. This study investigated the acute effects of the novel @entity10092 antagonist @entity42863 on motor behavior in L-Dopa-treated monkeys with a @entity5212 ( @entity5212 ) lesion to model @entity191 . Six @entity5434 @entity5212 monkeys were treated repeatedly with L-Dopa; this treatment increased their locomotion and reduced their @entity191 scores, but also induced @entity910 . When @entity42863 (doses of 5, 25, 125 or 250mg/kg) was administered one hour prior to a high dose of L-Dopa, the antiparkinsonian activity of L-Dopa was maintained as measured with locomotion and antiparkinsonian scores, whereas @entity910 were significantly reduced at 25, 125 and 250mg/kg @entity42863 for peak @entity910 score and at 125 and 250mg/kg for the 1h peak period of @entity910 score. Administration of @entity42863 one hour before L-Dopa led to peak or elevated plasma @entity42863 concentrations occurring close to L-Dopa peak-dose @entity910 . We next investigated @entity42863 25mg/kg combined with a low dose of L-Dopa. The antiparkinsonian activity of L-Dopa was increased as measured with locomotion, @entity910 remained low at these doses. Our results show a beneficial motor effect of @entity42863 with L-Dopa in @entity5212 monkeys. This supports the therapeutic use of an @entity10092 antagonist to restore normal glutamatergic neurotransmission in @entity191 and decrease @entity910 .
