Effects of 3-O-methyl on L-dopa-facilitated synthesis and efflux of dopamine from rat striatal slices.

1. The effect of L-dopa on the spontaneous and KCl-evoked efflux of dopamine from rat striatal slices, measured by high performance liquid chromatography (h.p.l.c.) with electrochemical detection (e.c.d.) was investigated in the absence and presence of 3-O-methyl dopa (OMD), an O-methylated metabolite of L-dopa. 2. The addition of exogenous L-dopa (10 microM) significantly increased both the spontaneous efflux of dopamine and that evoked by KCl. 3. In the presence of 50 microM OMD, the effects of L-dopa on the spontaneous and KCl-evoked efflux of dopamine were smaller but only the former was significantly different from that in the absence of OMD. However, the total efflux of dopamine during the overall superfusion time (70 min) including KCl depolarization was significantly lower than in the absence of OMD. 4. Analysis of tissue content after superfusion revealed that the levels of dopa and dopamine in slices superfused with L-dopa in the presence of OMD were significantly higher than those superfused with L-dopa alone. 5. The finding that OMD significantly reduced the efflux of dopamine whilst increasing its concentration in striatal slices after L-dopa superfusion could explain the reduced efficacy seen after long-term therapy with L-dopa and a peripheral dopa decarboxylase inhibitor in Parkinsonian patients when plasma and brain OMD are very high.