EFFECTS OF CHLORPROMAZINE ON THE METABOLISM OF dl-2-C¹⁴-DOPA IN THE RAT

¹ Medical Research Department, F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland

Albino rats received 20 mg/kg chlorpromazine intraperitoneally followed 30 minutes later by 20 mg/kg dl-2-C¹⁴-dopa subcutaneously. After a further 60 minutes the relative total radioactivity was measured in the fractions of amino acids, monoamines, and metabolic end products, such as phenolcarboxylic acids. The fractions of C¹⁴-amines and C¹⁴-phenolcarboxylic acids were further separated.

Chlorpromazine increased the three C¹⁴-fractions in the blood and decreased those in the urine if the animals were hypothermic. If, however, the chlorpromazine-induced hypothermia was prevented by an environmental temperature of 30.5°C, the drug no longer affected the blood values.

In the brain of both hypothermic and normothermic rats, chlorpromazine increased the overall radioactivity (radioactivity of the tissue extract before fractionation) mainly by a rise in the C¹⁴-phenolcarboxylic acids. In addition, the neuroleptic caused an absolute diminution of C¹⁴-norepinephrine and a percentage decrease of the fraction of C¹⁴-amines. Pretreatment with the monoamine oxidase inhibitor iproniazid prevented the chlorpromazine-induced increase in overall radioactivity and in C¹⁴-phenolcarboxylic acids.

Chlorprornazine increased the C¹⁴-phenolcarboxylic acids also in the heart and possibly in the adrenals. In the other organs, no effect of the drug was observed.

The present results suggest that in the rat brain in vivo chlorpromazine enhances the enzymatic inactivation of newly formed catecholamines, especially of norepinephrine. This effect, which is largely independent of hypothermia, may be due to a decrease in storage of the newly formed C¹⁴-amines.