Inhibition of rat brain tryptophan hydroxylation with p-chloroamphetamine

Abstract

p-Chloroamphetamine (PCA) at high concentrations (0.0025 to 0.02 M) inhibited rat brainstem tryptophan hydroxylase and, to a lesser extent, rat corpus striatum tyrosine hydroxylase. Hog kidney aromatic l-amino acid decarboxylase was not affected. Inhibition of tryptophan hydroxylase by p-chloroamphetamine was competitive with tryptophan and noncompetitive with 6,7-dimethyl-5,6,7,8-tetrahydropterine (DMPH 4). In rats given p-chloroamphetamine, brainstem tryptophan-hydroxylating activity was only slightly reduced, whereas striatal tyrosine-hydroxylating activity was not altered. Synthesis rates of brain serotonin and dopamine in rats treated with p-chloroamphetamine, estimated by measuring the accumulation of 5-hydroxytryptophan and dopa, respectively, after blockade of decarboxylase, were both decreased. In view of the high concentrations of p-chloroamphetamine required to inhibit tryptophan and tyrosine hydroxylases in vitro, mechanisms other than inhibition of enzyme by PCA might be responsible for the decelerated synthesis of serotonin and dopamine in brain (e.g. blockade of monoamine re-uptake).