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  • Title: Accumulation of chlorporomazine by subcellular fractions of rat brain.
    Author: Phillips E, Livingston A.
    Journal: Gen Pharmacol; 1976 Sep; 7(4):293-8. PubMed ID: 10227.
    Abstract:
    1. The study of the in vitro accumulation of [3H] chlorpromazine that a state of rapid equilibrium was reached for subcellular particles from cortex, midbrain and hindbrain of rats. 2. This accumulation was not saturable by increasing the concentration of chlorpromazine, and the relationship between accumulation and concentration was not modified by temperature, preincubation with high concentration of unlabelled chlorpromazine or by lowering the fraction concentration. 3. The highest accumulation of radioactivity was seen in the midbrain region and the lowest in the hindbrain. 4. In the cortex and midbrain the membrane fraction showed the highest accumulation. 5. The effect of pH on the accumulation indicated that a significnat rise was seen between pH 8 and 5. 6. This factor could also be explained in terms of solubility of the drug in membranes. 7. Studies on the metabolic fate of the drug during incubation indicated that there was a fairly rapid breakdown during incubation, the highest being seen with mitochondrail fractions and the least with membrane procedures. 9. It is concluded that accumulation of chlorpromazine by subcellular fractions in vitro may be associated with solubility in membranes and that the picture may be complicated by the presence of breakdown products.
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