Physicochemical analysis of the factors governing distribution of solutes between blood and brain

Abstract An equation is described that relates the equilibrium distribution of compounds between blood and brain to various solute descriptors, for 57 varied compounds. It is shown that the main factors influencing the distribution are solute size that favours brain, and solute dipolarity/polarisability, hydrogen-bond acidity and hydrogen-bond basicity that favour blood. The descriptors can be obtained from measurements on compound substructures, so that the blood-brain distribution can be predicted for drug molecules without the necessity for synthesis.

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