The effect of neuroleptics on brain tyrosine hydroxylase

The effect of a number of neuroleptics and tricyclic antidepressants on the activity of rat hypothalamic tyrosine hydroxylase was studied utilizing a direct spectrophotometric method. All the neuroleptics (but not the antidepressants) were able to reverse the substrate inhibition of the enzyme occurring when the tyrosine concentration in the medium was increased. Haloperidol, haloanisone and fluphenazine were found to activate the enzyme at optimal tyrosine concentrations in contrast to other neuroleptics which reduced the enzyme activity. The systemic administration of fluphenazine and clozapine was followed by an increase in the activity of striatal and hypothalamic tyrosine hydroxylase. The same drugs failed to produce this effect when administered chronically for 8 days.