Action of m-tyrosine in experimental models: Evidence for possible antiparkinsonian activity

Abstract

The antiparkinsonian acitivity of m-tyrosine was investigated in two experimental animal models. In rats with a unilateral 6-OH-dopamine (DA)-induced lesion of the nigro-neostriatal DA pathway, the administration of d,1- or 1-m-tyrosine in combination with an extracerebral 3,4-dihydroxyphenylalanine (Dopa) decarboxylase inhibitor or with a monoamine oxidase inhibitor causes marked turning of the rat towards the intact side and mimicks the action of Dopa in this model. The present results indicate that d,1- and 1-m-tyrosine treatment results in preferential stimulation of denervated DA receptors, the 1-form probably being the active form. Pharmacological analysis involving also cerebral decarboxylase inhibition, treatment with a DA-β-hydroxylase inhibitor or a DA-receptor blocking agent, spiroperidol, indicates that m-tyramine formed from m-tyrosine was acting as a false transmitter on Dd receptors. Negative results were obtained with α-methyl-Dopa, α-methyl-m-tyrosine and 5-hydropxyptophan (5-HTP), indicating that α-methyl-DA, α-methyl-m-tyrosine and 5-hydroxytryptamine (5-HT) are poor stimulators of DA-receptor sites. In monkeys with unilateral ventromedial tegmental lesions, d,1- and 1-m-tyrosine alone or in combination with an extracerebral Dopa-decarboxylase inhibitor causes a transient relief of the tremor of the ipsilateral extremities. The tremor relief induced by m-tyrosine but not only Dopa is potentiated when the animals are pretreated with a monoamine oxidase inhibitor. In both experimental models, m-tyrosine exhibited a weaker pharmacological activity than Dopa. The results suggest that m-tyrosine could be of therapeutic value in the treatment of Parkinsonism. Unlike Dopa, m-tyrosine is not metabolized by catechol-O-methyltransferase and, owing to its weaker DA-receptor stimulation could elicit less hyperk9nesias than Dopa.