INCORPORATION OF INORGANIC P32INTO PHOSPHOLIPIDS OF BRAIN SLICES: EFFECT OF CERTAIN TRANQUILLIZING DRUGS

Abstract

Promazine, promethazine, tetrameprazine, and WY 1172, four tranquillizing drugs that are derivatives of phenothiazine, resembled chlorpromazine in that when they were added in a concentration of 0.1 mM to slices of guinea pig brain respiring in a suitable medium they stimulated the incorporation of inorganic P32into the phospholipids of the slices. With one of the drugs, promethazine, this concentration of 0.1 mM was found to cause no significant increase in respiration, in aerobic glycolysis, or in the concentration of phosphocreatine. In higher concentrations (1.0 mM), all of the compounds inhibited the labelling of phospholipid. Promethazine caused a reduction in respiration and in the concentration of phosphocreatine, accompanied by an increase in aerobic glycolysis. Methylene blue, a derivative of phenothiazine with no reported tranquillizing properties, did not stimulate the labelling of phospholipid in brain slices. Azacyclonol, pipradrol, and mepazine, drugs that are derivatives of piperidine, also stimulated phospholipid labelling in low concentrations and inhibited the labelling at higher concentrations. Piperidine and benzhydrol, the two components from which azacyclonol is derived, did not stimulate phospholipid labelling at the concentration which was most effective for azacyclonol. Low concentrations of benzhydrol, however, caused a slight stimulation. Meprobamate and phenaglycodol, two other compounds with reputed tranquillizing action, had either little or no effect. Most of the substances tested inhibited phospholipid labelling when they were added in sufficiently high concentrations.