Objective: To assess the motor functions in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques following acute administration of AG-0029.

Background: Parkinson’s disease (PD), in which there is widespread degeneration of the catecholamine system, is characterized by motor symptoms and impairment of both cognitive performance and executive functions. A strategy to improve both types of symptoms might be to combine dopamine D2 receptor agonism, to alleviate motor symptoms, with histamine H3 receptor antagonism, to improve cognition. The purpose of the study was to examine the antiParkinsonian effects of such a dual activity compound in the gold standard primate model of PD, the so-called MPTP macaque model.

Methods: Parkinsonian symptoms were produced in 6 cynomolgus macaques by daily administration of MPTP (0.2 mg/kg, i.v.). Regular treatment with L-DOPA resulted in the development of dyskinesia. PD motor disability, dyskinesia and on-time were assessed following administration of AG-0029 (0.03, 0.1, 0.3 mg/kg) in comparison to L-DOPA and pramipexole.

Results: AG-0029 showed a full anti-Parkinsonian effect at 0.3 mg/kg with reduction of the disability, bradykinesia, posture scores and a long lasting effect of at least 10 hours. However, it induced also some dyskinesia as animals were primed. The 0.1 mg/kg dose produced a similar anti Parkinsonian effect to L-DOPA.

Conclusions: These results suggest the likely beneficial effects of AG-0029 on motor symptoms of PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/antiparkinsonian-effects-of-ag-0029-in-the-1-methyl-4-phenyl-1236-tetrahydropyridine-mptp-treated-macaque-model-of-parkinsons-disease/