D-512, a novel dopamine D2/3receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats
| Autor: | Melissa M. Conti, David Lindenbach, Aloke K. Dutta, Christopher Bishop, Samantha M. Meadows, Banibrata Das |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pharmacology Agonist Side effect medicine.drug_class Neuroprotection 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Ropinirole Dyskinesia Dopamine Dopamine receptor D2 medicine medicine.symptom Medial forebrain bundle Psychology 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | British Journal of Pharmacology. 174:3058-3071 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/bph.13937 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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