BLOCKADE OF ENDOGENOUS NOREPINEPHRINE SYNTHESIS BY ALPHA-METHYL-TYROSINE, AN INHIBITOR OF TYROSINE HYDROXYLASE.

Abstract

Repeated administration of the tyrosine hydroxylase inhibitor, α-methyl-tyrosine to guinea pigs decreased catecholamine levels in brain stem, caudate nucleus, heart and spleen to undetectable levels. Serotonin was unaffected. That the catecholamine decrease was a consequence of inhibition of tyrosine hydroxylase was shown by the following: tissue concentrations of norepinephrine failed to rise following monoamine oxidase inhibition and decarboxylase inhibitors failed to block the α-methyl-tyrosine effect; the conversion of tyrosine-C14 to norepinephrine was inhibited whereas that from dopa-H3 was not; and there was a normal uptake of exogenous norepinephrine by heart and spleen in animals pretreated with α-methyl-tyrosine. Preliminary studies of the pharmacologic consequences of blockade of norepinephrine synthesis indicate impairment of motor activity and mild sedation in cats and guinea pigs and a reduction of the tyramine and norepinephrine pressor responses in guinea pigs and rats.