In silico and in vitro evaluation of brain penetration properties of selected nootropic agents

Abstract

Aim: Predictive ( in silico) data suggested that nootropic supplements may penetrate the blood–brain barrier (BBB). We evaluated, in vitro, the ability of nootropics to enter the brain based on the high throughput screening (HTS) measurement of interactions with the P-gp efflux transporter and physicochemical properties and correlated these data with the in silico predictions. Methods & results: The software predicted that piracetam, docosahexaenoic acid (DHA), amantadine and thioflavin-T can best penetrate the BBB. The lipophilicity of these compounds may be predicted by measuring the critical micelle concentration (CMC). DHA and verapamil demonstrated high lipophilicity. DHA, verapamil and phosphatidylserine (PS) may be good substrates of the P-gp transporter. Conclusion: Permeability of nootropics may be successfully predicted by high throughput screening-lead optimization assay technologies.