INHIBITION OF NOREPINEPHRINE BIOSYNTHESIS BY CHLORPROMAZINE IN THE GUINEA-PIG VAS DEFERENS

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

Chlorpromazine decreased levels of norepinephrine-¹⁴C synthesized from tyrosine-¹⁴C in the guinea-pig vas deferens in vitro. The percent inhibition was unchanged during acceleration of the rate of synthesis induced by stimulation of the hypogastric nerve. Synthesis of norepinephrine-³H from 3,4-dihydroxyphenylalanine-³H and -methyloctopamine-³H from -methyltyramine-³H were also inhibited by chlorpromazine. Cocaine inhibited to a lesser extent norepinephrine-¹⁴C synthesis during stimulation and decreased the formation of -methyloctopamine-³H from -methyltyramine-³H. Neither chlorpromazine nor cocaine inhibited tyrosine hydroxylase or dopamine--hydroxylase activities measured in tissue homogenates. Although both chlorpromazine and cocaine diminished the uptake of norepinephrine-³H, neither drug influenced the proportion of the various metabohites of norepinephrine-³H found in the vasa deferentia. The drugs had no effect on the amounts of norepinephriue-¹⁴C formed from tyrosine-¹⁴C found in the incubation medium after nerve stimulation. These results suggest that chlorpromazine inhibits norepinephrme biosynthesis by blocking dopamine uptake into the nerve granules and that this inhibition remains proportionally the same during the increased rate of catecholamine synthesis obtained by nerve stimulation.