Protection of dopaminergic neurons in primary culture by lisuride

Dopamine agonists play an important role in the treatment of Parkinson's disease by reducing the administration of L-3,4-dihydroxyphenylalanine (L-DOPA). The enzymatic and non-enzymatic conversion of L-DOPA is suspected to increase oxidative stress, which leads to the degeneration of dopaminergic neurons in Parkinson's disease. In primary mouse mesencephalic cultures we show that the dopamine D1/D2 receptor agonist lisuride, in a concentration range of 0.001-1 microM, enhances the survival of dopaminergic neurons, protects against toxicity induced by L-DOPA or 1-methyl-4-phenylpyridinium ion (MPP+) and stimulates 3H-dopamine uptake. Lisuride also reduces anaerobic metabolism during incubation with L-DOPA. The present findings suggest that lisuride may have trophic/survival-promoting properties and potentially reduces oxidative stress.