ANTIPARKINSONIAN ACTIVITY OF TALIPEXOLE IN MPTP-TREATED MONKEYS - IN COMBINATION WITH L-DOPA AND AS CHRONIC TREATMENT

We examined whether or not the antiparkinsonian activity of talipexole (B-HT 920, ino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine) could b e optimised by combination with L-3,4-dihydroxyphenylalanine (L-DOPA). Additionally, the effects of chronic treatment with talipexole on mot or behavior were investigated using 1-methyl-4-phenyl-1,2,3,6-tetrahyd ropyridine (MPTP)-treated and normal common marmosets. Administration of MPTP (0.5 mg/animal i.v. once or twice) to marmosets induced persis tent parkinsonian motor deficits. The antiparkinsonian activity of tal ipexole (40 mu g/kg s.c.) was significantly enhanced by its combinatio n with L-DOPA (30 mg/kg i.p.). This may further support the postulated postsynaptic dopamine D-2 receptor agonist properties of talipexole. Chronic treatment with talipexole (a daily dose of 40 mu g/kg s.c. for 21 days) did not lead to tolerance to the antiparkinsonian activity i n MPTP-treated animals. No obvious dyskinesia was seen throughout the chronic treatment. In contrast, in normal marmosets, talipexole at a d ose of 80 mu g/kg which is a dose sufficient to induce hyperactivity d id not increase motor activity during the treatment repeated for 21 da ys. These results suggest that talipexole is a selective dopamine D-2 receptor agonist drug of potential use in the treatment of Parkinson's disease.