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

Autor: Erokhina PD; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia., Abalenikhina YV; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia., Mylnikov PY; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia., Petrov AV; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia., Ganina SO; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia., Konyakhin EA; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia., Shchulkin AV; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia. alekseyshulkin@rambler.ru., Yakusheva EN; Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia.
Jazyk: angličtina
Zdroj: Bulletin of experimental biology and medicine [Bull Exp Biol Med] 2023 Dec; Vol. 176 (2), pp. 170-175. Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1007/s10517-024-05989-1
Abstrakt: 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 /IC 50 ratio, showed that the effect of the tested substances on OATP1B1/OATP1B3 is clinically insignificant.
(© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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