Pharmaceutical Chemistry and Drug Design

One of the successes for CNS drugs is to penetrate the Blood-Brain Barrier (BBB) and achieve the therapeutic targets. Therefore, the rapid screening for potential BBB-penetration of drug candidates provides important information in early drug discovery research. The Parallel Artificial Membrane Permeability Assay (PAMPA) is a high-throughput screening tool applied to predict the passive transport of potential drugs across BBB. It is the non-cell-based in vitro assay often used in pharmaceutical industry which is carried out in a coated 96-well membrane filter. An artificial lipid membrane represented by the polar brain lipid is applied on a hydrophobic filter and the compounds are screened according to their pass from a Donor (D) compartment through the filter to an Acceptor (A) part. Subsequently, A and D wells are analyzed by LC/MS or in UV-Vis spectrophotometer. The assessed concentrations are then used for calculation of the permeability coefficient (Pe). Compounds with Pe lower than 2.0×10-6 cm.s-1 were classified as potentially non-BBB permeable (CNS-) and compounds with Pe higher than 4.0×10-6 cm.s-1 were recognized as potentially BBB permeable (CNS+). Of course, the assay can predict the CNS bioavailability based on the passive diffusion and active transport as well as efflux mechanisms are not considered. In the study, we correlated PAMPA-obtained permeability of some drugs (e.g. donepezil, rivastigmine, tacrine, testosterone, furosemide, sulfasalazine) and the results were compared with the real values mentioned in the literature.