In vitro and in silico evaluation of the interaction of yohimbine with drug transporters and cytochrome P450 isoenzymes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10512300" target="_blank" >RIV/00216208:11160/25:10512300 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=RH_W6tp-ss" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=RH_W6tp-ss</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2025.177869" target="_blank" >10.1016/j.ejphar.2025.177869</a>

Jazyk výsledku

angličtina

Název v původním jazyce

In vitro and in silico evaluation of the interaction of yohimbine with drug transporters and cytochrome P450 isoenzymes

Popis výsledku v původním jazyce

Yohimbine is a food supplement that is also used to treat erectile dysfunction. It has recently been introduced as a probe drug to assess the activity of cytochrome P450 (CYP) 2D6. This in vitro study investigated possible substrate and inhibitor properties of yohimbine for drug transporters and inhibitor properties for CYPs to assess, whether yohimbine might be prone to drug-drug interactions. Inhibition of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptides (OATPs) and organic cation transporters (OCTs) was tested by using probe substrates and transporter-overexpressing cell lines. The potential substrate properties of yohimbine for P-gp and OCTs were tested in accumulation assays in different cell lines with and without overexpression of the respective transporter. Inhibition of CYPs was assessed by using luminogenic substrates. The interaction of yohimbine with OCTs was evaluated in silico using docking analyses. Yohimbine did not inhibit P-gp, BCRP, OATP 1B1, 1B3 and 2B1. It was described and characterised in vitro and in silico as a good substrate of OCT1-3 (Km between 3.7 and 6.2 mu M) and a weak inhibitor of OCT2 and OCT3 with IC50 values in the upper micromolar range. Yohimbine potently inhibited CYP2D6 with an IC50 of 0.31 mu M, weakly inhibited CYP1A2, CYP2C19, and CYP3A4, and did not inhibit CYP2B6. In conclusion, we have verified that yohimbine inhibits CYP2D6 and demonstrated that it is a substrate of OCT1, OCT2, and OCT3, a weak inhibitor of OCT2 and OCT3, but does not inhibit P-gp, BCRP, OATP1B1, OTP1B3, OATP2B1, and OCT1.

Název v anglickém jazyce

In vitro and in silico evaluation of the interaction of yohimbine with drug transporters and cytochrome P450 isoenzymes

Popis výsledku anglicky

Yohimbine is a food supplement that is also used to treat erectile dysfunction. It has recently been introduced as a probe drug to assess the activity of cytochrome P450 (CYP) 2D6. This in vitro study investigated possible substrate and inhibitor properties of yohimbine for drug transporters and inhibitor properties for CYPs to assess, whether yohimbine might be prone to drug-drug interactions. Inhibition of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptides (OATPs) and organic cation transporters (OCTs) was tested by using probe substrates and transporter-overexpressing cell lines. The potential substrate properties of yohimbine for P-gp and OCTs were tested in accumulation assays in different cell lines with and without overexpression of the respective transporter. Inhibition of CYPs was assessed by using luminogenic substrates. The interaction of yohimbine with OCTs was evaluated in silico using docking analyses. Yohimbine did not inhibit P-gp, BCRP, OATP 1B1, 1B3 and 2B1. It was described and characterised in vitro and in silico as a good substrate of OCT1-3 (Km between 3.7 and 6.2 mu M) and a weak inhibitor of OCT2 and OCT3 with IC50 values in the upper micromolar range. Yohimbine potently inhibited CYP2D6 with an IC50 of 0.31 mu M, weakly inhibited CYP1A2, CYP2C19, and CYP3A4, and did not inhibit CYP2B6. In conclusion, we have verified that yohimbine inhibits CYP2D6 and demonstrated that it is a substrate of OCT1, OCT2, and OCT3, a weak inhibitor of OCT2 and OCT3, but does not inhibit P-gp, BCRP, OATP1B1, OTP1B3, OATP2B1, and OCT1.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmacology

ISSN

0014-2999

e-ISSN

1879-0712

Svazek periodika

1003

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

15

Strana od-do

177869

Kód UT WoS článku

001619145800001

EID výsledku v databázi Scopus

2-s2.0-105009298558