期刊
MOVEMENT DISORDERS
卷 25, 期 13, 页码 2059-2066出版社
WILEY
DOI: 10.1002/mds.23249
关键词
pardoprunox (SLV308); partial agonist; dyskinesia; levodopa; MPTP; Parkinson's disease
资金
- Solvay Pharmaceuticals Research Laboratories
- Parkinson's Disease Society
- National Parkinson Foundation, Miami
- Medical Research Council
- Gardiner Caldwell Communications (GCC) Macclesfield, UK
- Solvay Pharmaceuticals
- Alzheimer's Drug Discovery Foundation
Long-acting full dopamine D-2 agonists produce less dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates and in Parkinson's disease than effective antiparkinsonian doses of levodopa. They do not however, prevent priming for dyskinesia expression on subsequent levodopa exposure. In contrast, the effects of partial D-2 receptor agonists on dyskinesia are unclear. We now examine the ability of the partial D-2 agonist pardoprunox (SLV308) to improve motor function and its propensity to prime for dyskinesia in drug naive, MPTP-treated common marmosets. Previously, drug naive, MPTP-treated common marmosets were treated with equivalent doses of either pardoprunox (SLV308) (0.1 mg/kg po), ropinirole (0.18 mg/kg po), or levodopa (10 mg/kg po BID) for 28 days. All treatments induced a similar reduction of motor disability. Dyskinesia induced by levodopa was of greater intensity than that following administration of either pardoprunox (SLV308) or ropinirole. Administration of pardoprunox (SLV308) resulted in dyskinesia that was less intense and of shorter duration than either ropinirole or levodopa. At the end of drug treatment, acute challenge with levodopa resulted in the expression of marked dyskinesia in animals that had previously received chronic levodopa or ropinirole treatment. However, animals previously treated with pardoprunox (SLV308) showed only mild dyskinesia in response to the levodopa challenge. These results suggest that the partial D-2 agonist pardoprunox (SLV308) is less likely to prime for dyskinesia or to lead to the expression of dyskinesia than either levodopa or full dopamine agonists. (C) 2010 Movement Disorder Society
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