Dataset Information

D-512, a novel dopamine D_2/3 receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.

ABSTRACT:

Background and purpose

Symptoms of Parkinson's disease are commonly managed using selective dopamine D_2/3 receptor agonists, including ropinirole. While D_2/3 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 D_2/3 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 D_2/3 agonists and could merit clinical investigation.

SUBMITTER: Lindenbach D

PROVIDER: S-EPMC5573415 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

D-512, a novel dopamine D<sub>2/3</sub> receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.

Lindenbach David D Das Banibrata B Conti Melissa M MM Meadows Samantha M SM Dutta Aloke K AK Bishop Christopher C

British journal of pharmacology 20170811 18

<h4>Background and purpose</h4>Symptoms of Parkinson's disease are commonly managed using selective dopamine D<sub>2/3</sub> receptor agonists, including ropinirole. While D<sub>2/3</sub> 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 D<sub>2/3</sub> receptor agonist with antioxidant and other neuroprote ...[more]

PMID: 28667675

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Dataset Information

D-512, a novel dopamine D_2/3 receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

D-512, a novel dopamine D<sub>2/3</sub> receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

D-512, a novel dopamine D<sub>2/3</sub> receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

D-512, a novel dopamine D_2/3 receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.