ANTI-TREMOR ACTIVITY OF TALIPEXOLE PRODUCED BY SELECTIVE DOPAMINE D-2RECEPTOR STIMULATION IN CYNOMOLGUS MONKEYS WITH UNILATERAL LESIONS INTHE VENTROMEDIAL TEGMENTUM

The anti-tremor activity of talipexole amino-5,6,7,8-tetrahydro-4H-thi azolo[4,5-d]azepine dihydrochloride, B-HT 920 CL(2), Domin), a non-erg ot dopamine D-2 receptor agonist which possesses alpha(2)-adrenoceptor agonistic and 5-HT3 receptor antagonistic properties, was examined in monkeys with a unilateral lesion in the ventromedial tegmentum. Talip exole dose dependently suppressed the tremor and had ED(50) values of 34 mu g/kg s.c. and 84 mu g/kg p.o. The anti-tremor effect of talipexo le occurred at much lower doses than that of an ergot dopamine recepto r agonist, bromocriptine (2-bromo-alpha-ergocryptine mesilate, ED(50); 2.5 mg/kg s.c.), and talipexole acted synergistically in combination with L-DOPA (3,4-dihydroxyphenylalanine). In ventromedial tegmentum-le sioned monkeys, anti-tremor doses of talipexole did not cause emetic b ehavior, but had sedative effects. Conversely, monkeys given bromocrip tine exhibited oral movement, salivation and vomiting when anti-tremor effects were observed, but not marked sedative behavior at any of the doses investigated. During repeated administration of talipexole (a d aily dose of 50 mu g/kg s.c. for 21 days), the extent and duration of the anti-tremor effect did not change, but those of the sedative effec t decreased gradually. The anti-tremor effect of talipexole was signif icantly suppressed by sulpiride, but not by SCH 23390 etrahydro-3-meth yl-5-phenyl-1H-3-benzazepine-7-ol) or yohimbine, while the sedative ef fect was inhibited by sulpiride and yohimbine. The main metabolites of talipexole had no anti-tremor or sedative effects. These results indi cate that talipexole exerts its anti-tremor activity via selective dop amine D, receptor stimulation.