Conjugation of Synthetic Cannabinoids JWH-018 and JWH-073, Metabolites by Human UDP-Glucuronosyltransferases

• DOI: 10.1124/dmd.111.040709
• Publication Date: 2011-07-12T06:10:11Z
• Authors: Krishna C. Chimal...; Stacie M. Bratton; Vi-Huyen Le; Kan Hui Yiew; Anna Dineva; Cindy L. Moran; Laura P. James; Jeffery H. Moran; Anna Radominska-P...
• Keywords: Synthetic cannabinoids

K2, a synthetic cannabinoid (SC), is an emerging drug of abuse touted as "legal marijuana" and marketed to young teens first-time users. Symptoms associated with K2 use include extreme agitation, syncope, tachycardia, visual auditory hallucinations. One major challenge clinicians the lack clinical, pharmacological, metabolic information for detection characterization its metabolites in human samples. Information on pathway SCs very limited. However, previous reports have shown these compounds are excreted primarily glucuronic acid conjugates. Based this information, study evaluates nine recombinant uridine diphosphate-glucuronosyltransferase (UGT) isoforms liver intestinal microsomes their ability glucuronidate hydroxylated 1-naphthalenyl-1(1-pentyl-1<i>H</i>-indol-3-yl)-methanone (JWH-018) (1-butyl-1<i>H</i>-indol-3-yl)-1-naphthalenyl-methanone (JWH-073), two most common found products. Conjugates were identified characterized using liquid chromatography/tandem mass spectrometry, whereas kinetic parameters quantified high-performance chromatography-UV-visible methods. UGT1A1, UGT1A3, UGT1A9, UGT1A10, UGT2B7 be enzymes involved, showing relatively high affinity <i>K</i>_m ranging from 12 18 μM some K2s. These UGTs also exhibited capacity compounds, which indicates that may rapidly glucuronidated eliminated body. Studies will help future development validation specific assay allow researchers fully explore pharmacological actions.