In vitro blood–brain barrier permeability predictions for GABAA receptor modulating piperine analogs - Université d'Artois Access content directly
Journal Articles European Journal of Pharmaceutics and Biopharmaceutics Year : 2016

In vitro blood–brain barrier permeability predictions for GABAA receptor modulating piperine analogs

Abstract

The alkaloid piperine from black pepper (Piper nigrum L.) and several synthetic piperine analogs were recently identified as positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors. In order to reach their target sites of action, these compounds need to enter the brain by crossing the blood-brain barrier (BBB). We here evaluated piperine and five selected analogs (SCT-66, SCT-64, SCT-29, LAU397, and LAU399) regarding their BBB permeability. Data were obtained in three in vitro BBB models, namely a recently established human model with immortalized hBMEC cells, a human brain-like endothelial cells (BLEC) model, and a primary animal (bovine endothelial/rat astrocytes co-culture) model. For each compound, quantitative UHPLC-MS/MS methods in the range of 5.00-500ng/mL in the corresponding matrix were developed, and permeability coefficients in the three BBB models were determined. In vitro predictions from the two human BBB models were in good agreement, while permeability data from the animal model differed to some extent, possibly due to protein binding of the screened compounds. In all three BBB models, piperine and SCT-64 displayed the highest BBB permeation potential. This was corroborated by data from in silico prediction. For the other piperine analogs (SCT-66, SCT-29, LAU397, and LAU399), BBB permeability was low to moderate in the two human BBB models, and moderate to high in the animal BBB model. Efflux ratios (ER) calculated from bidirectional permeability experiments indicated that the compounds were likely not substrates of active efflux transporters.
Fichier principal
Vignette du fichier
Opens access manuscript.pdf (1.23 Mo) Télécharger le fichier
Origin Files produced by the author(s)

Dates and versions

hal-02510088 , version 1 (09-07-2022)

Identifiers

Cite

Daniela Elisabeth Eigenmann, Carmen Dürig, Evelyn Andrea Jähne, Martin Smieško, Maxime Culot, et al.. In vitro blood–brain barrier permeability predictions for GABAA receptor modulating piperine analogs. European Journal of Pharmaceutics and Biopharmaceutics, 2016, 103, pp.118-126. ⟨10.1016/j.ejpb.2016.03.029⟩. ⟨hal-02510088⟩

Collections

UNIV-ARTOIS LBHE
147 View
19 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More