Testing the Protective Effects of Sulfobutylether-Βeta-Cyclodextrin (SBECD) and Sugammadex Against Chlorpromazine-Induced Acute Toxicity in SH-SY5Y Cell Line and in NMRI Mice

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Sep 23

PMID 36145637

Authors

Eszter Fliszar-Nyul

Rita Csepregi

Gabor Benkovics

Lajos Szente

Miklos Poor

Affiliations

Soon will be listed here.

Abstract

Chlorpromazine (CPZ) is an antipsychotic drug which can cause several adverse effects and drug poisoning. Recent studies demonstrated that CPZ forms highly stable complexes with certain cyclodextrins (CDs) such as sulfobutylether-β-CD (SBECD) and sugammadex (SGD). Since there is no available antidote in CPZ intoxication, and considering the good tolerability of these CDs even if when administered parenterally, we aimed to investigate the protective effects of SBECD and SGD against CPZ-induced acute toxicity employing in vitro (SH-SY5Y neuroblastoma cells) and in vivo (zebrafish embryo) models. Our major findings and conclusions are the following: (1) both SBECD and SGD strongly relieved the cytotoxic effects of CPZ in SH-SY5Y cells. (2) SGD co-treatment did not affect or increase the CPZ-induced 24 h mortality in NMRI mice, while SBECD caused a protective effect in a dose-dependent fashion. (3) The binding constants of ligand-CD complexes and/or the in vitro protective effects of CDs can help to estimate the in vivo suitability of CDs as antidotes; however, some other factors can overwrite these predictions.

Citing Articles

Advancements in cyclodextrin-based controlled drug delivery: Insights into pharmacokinetic and pharmacodynamic profiles.

Neaz S, Alam M, Imran A Heliyon. 2024; 10(21):e39917.

PMID: 39553547 PMC: 11567044. DOI: 10.1016/j.heliyon.2024.e39917.

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