6533b7d2fe1ef96bd125e083

RESEARCH PRODUCT

Effects of chlorpromazine and some of its metabolites on the EEG and on dopamine metabolism of the isolated perfused rat brain.

subject

description

Abstract The study concerned the effects of chlorpromazine (CPZ), monodesmethyl-chlorpromazine (NOR1-CPZ), didesmethyl-chlorpromazine (NOR2-CPZ), and chlorpromazine-N-oxide (CPZ-NO) on the EGG and on dopamine metabolism of the isolated perfused rat brain. Isolated brains were perfused with 100 ml of a perfusion medium containing 30% bovine red cells (v/v), 2 g bovine serum albumin, 14 mM glucose as well as one of the agents in a concentration of 10 μM. The main dopamine metabolite homovanillic acid (HVA) was measured fluorimetrically in the striatum of the isolated brain. The EGG was recorded by two symmetrical bipolar leads from the parietal regions at various times during the 30 min perfusion period and was stored on magnetic tape. The recording were evaluated visually and quantitatively by automatic analysis. CPZ-NO was found to be the most active agent both in changing the EGG and in elevating the HVA level in the striatum. The mean EGG amplitude and the slow wave activity increased significantly. The increase of the HVA level in the striatum was correlated with the increase of delta waves as well as excess of kurtosis and skewness calculated from the amplitude histography data. The desmethylated metabolites caused only moderate central effects.