Preladenant, a selective A(2A) receptor antagonist, is active in primate models of movement disorders

Experimental Neurology
Robert A HodgsonJohn Hunter

Abstract

Parkinson's Disease (PD) and Extrapyramidal Syndrome (EPS) are movement disorders that result from degeneration of the dopaminergic input to the striatum and chronic inhibition of striatal dopamine D(2) receptors by antipsychotics, respectively. Adenosine A(2A) receptors are selectively localized in the basal ganglia, primarily in the striatopallidal ("indirect") pathway, where they appear to operate in concert with D(2) receptors and have been suggested to drive striatopallidal output balance. In cases of dopaminergic hypofunction, A(2A) receptor activation contributes to the overdrive of the indirect pathway. A(2A) receptor antagonists, therefore, have the potential to restore this inhibitor imbalance. Consequently, A(2A) receptor antagonists have therapeutic potential in diseases of dopaminergic hypofunction such as PD and EPS. Targeting the A(2A) receptor may also be a way to avoid the issues associated with direct dopamine agonists. Recently, preladenant was identified as a potent and highly selective A(2A) receptor antagonist, and has produced a significant improvement in motor function in rodent models of PD. Here we investigate the effects of preladenant in two primate movement disorder models. In MPTP-treated cynomolgu...Continue Reading

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