Session Time: 12:00pm-1:30pm
Objective: Investigate a combination of two clinically tested drugs, the NR2B antagonist Radiprodil and the A2A antagonist Tozadenant in unilaterally 6-OHDA-lesioned rats and in MPTP-treated marmosets.
Background: In Parkinson’s disease, there remains a need for the development of non-dopaminergic drugs to effectively treat the motor symptoms without the induction of abnormal motor complications.
Methods: Radiprodil and Tozadenant were given both alone and in combination without the addition of L-dopa, and the antiParkinsonian efficacy of the treatments were compared in both rat and primate models.
Results: In both species, the drug combination led to a significant increase of motor activity and an improvement in motor disability compared with monotherapy. In addition, in the MPTP-treated marmosets, the motor restoration afforded by the “Radiprodil/Tozadenant” combination was devoid of any dyskinesia. Interestingly we noticed that primates, unlike rodents, were not overstimulated, but were able to move normally when motivated by the exploration of novel objects.
Conclusions: This report confirms in a bilateral primate model of Parkinson’s disease, the remarkable motor improvements previously observed in unilaterally lesioned 6-OHDA-rats treated with the “Radiprodil/Tozadenant” combination. The strength of the preclinical data accumulated thus far strongly suggests that the use of this combination could bring significant motor improvement to Parkinson’s disease patients. Furthermore, our data suggest that this could be achieved without inducing the abnormal movements which are characteristic of chronic dopaminergic therapy. If these results were to be validated in a clinical study, it would make a strong case for considering the combined administration of an A2A and an NR2B antagonist for the symptomatic treatment of Parkinsonian patients.
To cite this abstract in AMA style:A. Michel, J.M. Nicolas, S. Rose, M. Jackson, P. Colman, W. Briône, D. Sciberras, P. Muglia, D. Scheller, M. Citron, P. Downey. AntiParkinsonian effects of the “radiprodil and tozadenant” combination in MPTP-treated marmosets [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/antiparkinsonian-effects-of-the-radiprodil-and-tozadenant-combination-in-mptp-treated-marmosets/. Accessed March 2, 2024.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/antiparkinsonian-effects-of-the-radiprodil-and-tozadenant-combination-in-mptp-treated-marmosets/