EFFECTS OF 3-O-METHYL DOPA ON L-DOPA-FACILITATED SYNTHESIS AND EFFLUXOF DOPAMINE FROM RAT STRIATAL SLICES

1 The effect of L-dopa on the spontaneous and KCl-evoked efflux of dop amine from rat striatal slices, measured by high performance liquid ch romatography (h.p.l.c.) with electrochemical detection (e.c.d.) was in vestigated 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 mu M) significantly increased both the spontaneous efflux of dopamine and that evoked by KCI. 3 In the presence of 50 mu M OMD, the effects of L-dopa on the spontaneous and KCl-evoked efflux of dopamine were s maller but only the former was significantly different from that in th e absence of OMD. However, the total efflux of dopamine during the ove rall superfusion time (70 min) including KCI depolarization was signif icantly lower than in the absence of OMD. 4 Analysis of tissue content after superfusion revealed that the levels of dopa and dopamine in sl ices 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 co ncentration in striatal slices after L-dopa superfusion could explain the reduced efficacy seen after long-term therapy with L-dopa and a pe ripheral dopa decarboxylase inhibitor in Parkinsonian patients when pl asma and brain OMD are very high.