Block of Cerebral Actions of L -Dopa with Methyl Receptor Substances

AFTER sufficient L -dopa was administered to patients with Parkmsonism 1,2 it was found that a large proportion of the labile methyl groups supplied in their diets was excreted as homovanillic acid (HVA) 2 . The resulting control of Parkinsonism was sometimes marred by episodes of “freezing” while walking 1,2 . Such episodes were reduced by co-administration of the peripheral decarboxylase inhibitor α-methyl-dopa hydrazine (MK-485) which potentiates clinical effects of L -dopa 2 . The inhibitor has diminished, however, the proportion of L -dopa recovered as HVA in experiments to be discussed elsewhere. If HVA could block cerebral effects of L -dopa, its diminution could have contributed to the potentiation of L -dopa by the inhibitor. Experimental pursuit of this hypothesis in mice led to radically different conclusions.