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

Abstract

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-dopa². 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.