The factors that influence permeation across the blood-brain barrier

Using data on perfusion from saline at pH 7.4 taken from the literature, it is shown that logarithms of PS-products, log PS, can satisfactorily be correlated with the five Abraham descriptors for 30 neutral compounds. The equation has R(2) = 0.870 and S.D. = 0.52, and shows that molecular size leads to an increase in permeation rate, and dipolarity/polarizability, hydrogen bond acidity and hydrogen bond basicity all decrease the rate of permeation. There are difficulties with acids and bases that are partially ionised at pH 7.4 because it is not possible to assess the rate of permeation of the resulting ionic species with respect to the neutral species. The same problem will arise in the analysis of perfusion from plasma or blood.