Session Information
Date: Thursday, June 23, 2016
Session Title: Neuropharmacology
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To assess the cognitive 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 both 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 cognitive effects of such a dual activity compound in the gold standard primate model of cognitive defects in PD, the so-called chronic low-dose (CLD) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) macaque model.
Methods: Cognitive performances were assessed in 3 behavioural tasks following administrations of AG-0029 (0.03, 0.1 or 0.3 mg/kg). Four CLD cynomolgus macaques, displaying cognitive deficits and mild Parkinsonian motor deficits, produced by chronic exposure to low doses of MPTP were tested in the Variable Delayed Response (VDR) and the Continuous Performance Task (CPT) on a touch-screen computerized system. Eight MPTP cynomolgus macaques, displaying more severe motor deficits, were tested in the Object Retrieval (OR) task.
Results: In the OR task, AG-0029 at 0.1 mg/kg significantly improved 1st attempt successes and correct responses by decreasing omissions compared to an optimal dose of L-DOPA. No significant overall effect of AG-0029 was found on the VDR tasks. However, when performing a best dose analysis, AG-0029 significantly improved the percentages of correct responses and decreased errors compared to vehicle in the VDR. In the CPT, AG-0029 did not show any positive effects.
Conclusions: AG-0029 improved cognitive performance of MPTP-treated monkeys in the OR and VDR tasks but not in the CPT. These results suggest the likely beneficial cognitive effects of AG-0029 for patients with PD-mild cognitive impairments.
To cite this abstract in AMA style:
E.Y. Pioli, S.M.J. Camus, J. Yang, Q. Li, A. Crossman, E. Bezard, S. Hogg. Cognitive effects of AG-0029 in the chronic low-dose (CLD) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/cognitive-effects-of-ag-0029-in-the-chronic-low-dose-cld-1-methyl-4-phenyl-1236-tetrahydropyridine-mptp-treated-macaque-model-of-parkinsons-disease/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-effects-of-ag-0029-in-the-chronic-low-dose-cld-1-methyl-4-phenyl-1236-tetrahydropyridine-mptp-treated-macaque-model-of-parkinsons-disease/