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Br J Pharmacol. 2017 Sep;174(18):3058-3071. doi: 10.1111/bph.13937. Epub 2017 Aug 11.

D-512, a novel dopamine D2/3 receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.

Author information

1
Behavioral Neuroscience Program, Department of Psychology, Binghamton University - State University of New York, Binghamton, NY, USA.
2
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.

Abstract

BACKGROUND AND PURPOSE:

Symptoms of Parkinson's disease are commonly managed using selective dopamine D2/3 receptor agonists, including ropinirole. While D2/3 agonists are useful in early-stage Parkinson's disease, they tend to lose efficacy in later disease stages and do not appear to modify disease progression. We have recently developed a novel 'multifunctional' compound, D-512: a high-affinity D2/3 receptor agonist with antioxidant and other neuroprotective properties that may limit Parkinson's disease progression. This study sought to compare the anti-Parkinsonian properties of the clinically used compound, ropinirole, with those of the novel compound, D-512.

EXPERIMENTAL APPROACH:

A rat model of Parkinson's disease was created by unilaterally infusing 6-hydroxydopamine, a dopamine neurotoxin, into the medial forebrain bundle. D-512 was compared with ropinirole for ability to stimulate spontaneous motor activity and reverse Parkinsonian akinesia. These beneficial effects were compared against each drug's liability to provoke dyskinesia, a common motor side effect.

KEY RESULTS:

Both compounds increased spontaneous movement, but D-512 showed a longer duration of action. Only D-512 was able to significantly reverse forelimb akinesia. Drug-induced dyskinesia was similar for equivalent doses.

CONCLUSIONS AND IMPLICATIONS:

Compared with ropinirole, D-512 showed greater peak-dose efficacy and a longer duration of action, despite a similar side-effect profile. Our results add to earlier data showing that D-512 is superior to available D2/3 agonists and could merit clinical investigation.

PMID:
28667675
PMCID:
PMC5573415
DOI:
10.1111/bph.13937
[Indexed for MEDLINE]
Free PMC Article

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