Printed in JJS.A EFFECT OF CHLORPROMAZINE ON ACCTJMIJLATION AND DISAPPEARANCE OF CATECHOLAMINES FORMED FROM TYROSINE-C14 IN BRAIN”2

NYBACK, HENRIK AND G#{246}RANSEDVALL: Effect of chlorpromazine on accumulation and disappearance of catecholamines formed from tyrosine-C ” in brain. J. Pharmacol. Exp. Therap. 162: 294-301, 1968. Tyrosine-C ” was administered to nonanesthetized rats and mice by i.v. injection or constant-rate infusion during 20 mm. The effect of chlorpromazine on the rates of accumulation and disappearance of labeled noradrenaline and dopamine was determined. After chlorpromazine the accumulation of dopamine-C1 ’ in brain was in-creased up to 3-fold in both species. The effect was dose-dependent, was evident within #{189} hr after the drug administration and lasted for about 10 hr. Only in rats and only at the highest dosage used (25 mg/kg) was an increased accumulation of noradrenaline-C1’ found. After chronic chiorpromazine treatment similar results were obtained. After pre-labeling of the brain catecholamine stores by administration of tyrosine-C14, chiorpromazine significantly increased the rate of disappearance of dopamine-C1 ’ but not that of nor-adrenaline-C14. The specific activity of tyrosine-C1 ’ was not significantly altered by chlorpromazine. The results suggest that chlorpromazine accelerates synthesis and turnover of brain dopamine, possibly by blocking central dopamine receptors. Chlorpromazine produces a behavioral syn-drome similar to that seen after reserpine. In contrast to the latter drug chiorpromazine has little or no effect on brain monoamine level