Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS.
The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high binding affinity at the peripheral cannabinoid receptor CB(2), has been studied. A total of 22 metabolites were identified and structurally characterized. The metabolites are products of: 1) monohydroxylation on the naphthalene ring (m/z 344, M20 and M21), indole ring (m/z 344, M17 and M18), or the N-alkyl group (m/z 344, M14); 2) arene oxidation leading to dihydrodiols (m/z 362, M12 and M15); 3) dihydroxylation on the naphthalene ring (m/z 360, M7) or indole ring (m/z 360, M13), resulting from a combination of monohydroxylations on both the naphthalene and indole rings (m/z 360, M16), or a combination of monohydroxylations on the naphthalene ring and on the N-propyl group (m/z 360, M9); 4) trihydroxylation (m/z 378, M1, M3, M4, M6, and M10); 5) N-dealkylation (m/z 286, M19); 6) N-dealkylation and monohydroxylation on the naphthalene ring (m/z 302, M11); 7) N-dealkylation and dihydrodiol formation from arene oxidation (m/z 320, M2 and M5); 8) dehydrogenation after monohydroxylation on the N-alkyl group (m/z 326, M22); 9) dehydrogenation and monohydroxylation on the indole ring (m/z 342, M8).
Zhang
Qiang
Q
Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Ma
Peng
P
Cole
Richard B
RB
Wang
Guangdi
G
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D007211:Indoles / Q000819:agonists* / Q000032:analysis / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; C402944:JHW 015