The Effect of Original Russian Neurotropic Drugs on Organic Anion Transporting Polypeptides OATP1B1 and OATP1B3

In experiments on HepG2 cells, we studied the effect of the original domestic neurotropic drugs omberacetam, fabomotizole, and ethylmethylhydroxypyridine succinate (EMHPS) (1-500 μM) on the activity and content of organic anion transporting polypeptides OATP1B1 and OATP1B3. It was shown that omberacetam (500 μM) increased the content of OATP1B1 and OATP1B3, fabomotizole did not affect the level of both transporters, and EMHPS (500 μM) increased the content of OATP1B1 compared to the control and did not affect the level of OATP1B3. The tested substances also reduced the OATP1B1/OATP1B3 ratio, as evidenced by a decrease in the penetration of atorvastatin, a substrate of the transporters, into HepG2 cells in the presence of omberacetam (100-500 μM), fabomotizole (500 μM), and EMHPS (10-500 μM). Evaluation of clinical significance of the obtained results, according to the FDA approach based on the calculation of the C_max/IC₅₀ ratio, showed that the effect of the tested substances on OATP1B1/OATP1B3 is clinically insignificant.