Investigative analysis of blood–brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models

Authors: Stratford K, Kang JC, Healy SM, Tu Z, Valerio LG Jr
Publication: Expert Opin Drug Metab Toxicol
Keywords: adme prediction, admet predictor, bbb prediction, chemical risk assessment, high throughput pharmacokinetics, HTPK, machine learning, partition coefficients, swiftpk, transporters
Software: ADMET Predictor®
Division: Cheminformatics

Abstract

Seizures are known potential side effects of nicotine toxicity and have been reported in electronic nicotine delivery systems (ENDS, e-cigarettes) users, with the majority involving youth or young adults.

Areas Covered

Using chemoinformatic computational models, chemicals (including flavors) documented to be present in ENDS were compared to known neuroactive compounds to predict the blood–brain barrier (BBB) penetration potential, central nervous system (CNS) activity, and their structural similarities. The literature search used PubMed/Google Scholar, through September 2023, to identify individual chemicals in ENDS and neuroactive compounds.

The results show that ENDS chemicals in this study contain >60% structural similarity to neuroactive compounds based on chemical fingerprint similarity analyses. The majority of ENDS chemicals we studied were predicted to cross the BBB, with approximately 60% confidence, and were also predicted to have CNS activity; those not predicted to passively diffuse through the BBB may be actively transported through the BBB to elicit CNS impacts, although it is currently unknown.

Expert Opinion
In lieu of in vitro and in vivo testing, this study screens ENDS chemicals for potential CNS activity and predicts BBB penetration potential using computer-based models, allowing for prioritization for further study and potential early identification of CNS toxicity.

By Kimberly Stratford, Jueichuan Connie Kang,Sheila M. Healy,Zheng Tu &Luis G. Valerio Jr.