Detection and Characterization of the Effect of AB-FUBINACA and Its Metabolites in a Rat Model

• Published in: Journal of cellular biochemistry Vol. 117; no. 4; pp. 1033 - 1043
• Main Authors: Hsin-Hung Chen, Michael, Dip, Aybike, Ahmed, Mostafa, Tan, Michael L., Walterscheid, Jeffrey P., Sun, Hua, Teng, Ba-Bie, Mozayani, Ashraf
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.04.2016; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: AB-FUBINACA; Animal models; Animals; Biocompatibility; Biotransformation; Cannabinoids; Cannabinoids - pharmacokinetics; Cannabinoids - urine; Cardiotoxicity; Degenerative diseases; Designer Drugs - pharmacokinetics; Forensic science; GENE EXPRESSION; Gene Expression Profiling; Gene Expression Regulation - drug effects; Heart; Heart - drug effects; Hepatocytes; Hepatotoxicity; In vivo methods and tests; Indazoles - pharmacokinetics; Indazoles - urine; Inflammation; Liver; Liver - drug effects; Liver - metabolism; Mass spectrometry; Mass spectroscopy; Metabolites; Metabolome; Organs; Oxidation; Pain; Pharmacology; Public health; RAT; Rats; Rats, Wistar; Recreational drugs; SYNTHETIC CANNABINOIDS; Toxicology; URINE; GENE EXPRESSION; RAT; SYNTHETIC CANNABINOIDS; AB-FUBINACA; URINE
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25421

ABSTRACT Synthetic cannabinoids were originally developed by academic and pharmaceutical laboratories with the hope of providing therapeutic relief from the pain of inflammatory and degenerative diseases. However, recreational drug enthusiasts have flushed the market with new strains of these potent drugs that evade detection yet endanger public health and safety. Although many of these drug derivatives were published in the medical literature, others were merely patented without further characterization. AB‐FUBINACA is an example of one of the new indazole‐carboxamide synthetic cannabinoids introduced in the past year. Even though AB‐FUBINACA has become increasingly prominent in forensic drug and toxicology specimens analyses, little is known about the pharmacology of this substance. To study its metabolic fate, we utilized Wistar rats to study the oxidative products of AB‐FUBINACA in urine and its effect on gene expressions in liver and heart. Rats were injected with 5 mg/kg of AB‐FUBINACA each day for 5 days. Urine samples were collected every day at the same time. On day 5 after treatment, we collected the organs such as liver and heart. The urine samples were analyzed by mass spectrometry, which revealed several putative metabolites and positioning of the hydroxyl addition on the molecule. We used quantitative PCR gene expression array to analyze the hepatotoxicity and cardiotoxicity on these rats and confirmed by real‐time quantitative RT‐PCR. We identified three genes significantly associated with dysfunction of oxidation and inflammation. Our study reports in vivo metabolites of AB‐FUBINACA in urine and its effect on the gene expressions in liver and heart. J. Cell. Biochem. 117: 1033–1043, 2016. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals. Inc.