N-METHYL-4-PHENYLPYRIDINIUM AND AN ENDOGENOUSLY FORMED ANALOG, N-METHYLATED BETA-CARBOLINIUM, INHIBIT STRIATAL TYROSINE HYDROXYLATION IN FREELY MOVING RATS

The effects of N-methyl-4-phenylpyridinium (MPP(+)) and its endogenous analog, 2,9-di-methyl-norharmanium (2,9-Me(2)NH(+)), on in vivo tyros ine hydroxylation were evaluated in freely moving rats. MPP(+) gradual ly but almost completely reduced tyrosine hydroxylation, even at a dos e as low as 0.05 mM. This effect was considered to be caused by the in hibition of tyrosine hydroxylase (TH) activation. On the contrary, 1 m M 2,9-Me(2)NH(+) rapidly reduced 3,4-dihydroxyphenylalanine production to 10% of the basal level only during its perfusion, indicating direc t inhibition of TH activity. The present study revealed that MPP(+) an d 2,9-Me(2)NH(+) were taken up into dopaminergic neurons and then inhi bited in vivo dopamine synthesis prior to cell death possibly in diffe rent manners.