Universität zu Köln

Wintermeyer, Annette, Moeller, Ines, Thevis, Mario, Juebner, Martin, Beike, Justus, Rothschild, Markus A. and Bender, Katja (2010). In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. Anal. Bioanal. Chem., 398 (5). S. 2141 - 2154. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1618-2650

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Abstract

A potent synthetic cannabinoid receptor agonist, JHW-018, was recently detected as one of the most prominent active agents in abusively used incenses such as Spice and other herbal blends. The high pharmacological and addictive potency of JWH-018 highlights the importance of elucidating the metabolism of JWH-018, without which a meaningful insight into its pharmacokinetics and its toxicity would not be possible. In the present study, the cytochrome P450 phase I metabolites of JWH-018 were investigated, after in vitro incubation of the drug with human liver microsomes, followed by liquid chromatography-tandem mass spectrometry analysis. This revealed monohydroxylation of the naphthalene ring system, the indole moiety, and the alkyl side chain. In addition, observations were made of dihydroxylation of the naphthalene ring system, and the indole moiety, or as result of a combination of monohydroxylations of both the naphthalene ring system and the indole moiety or the alkyl side chain, or a combination of monohydroxylations of both the indole ring system and the alkyl side chain. There is also evidence of trihydroxylation at different locations of the hydroxyl groups in the molecule. Furthermore, dehydration of the alkyl side chain, in combination with both monohydroxylation and dihydroxylation as well as arene oxidation of the naphthalene ring system, combined with both monohydroxylation and dihydroxylation at different sites of oxidation were found. N-dealkylation also in combination with both monohydroxylation and dihydrodiol formation of the N-dealkylated metabolite was detected. Finally, a metabolite was found carboxylated at the alkyl side chain.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wintermeyer, Annette UNSPECIFIED UNSPECIFIED UNSPECIFIED Moeller, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Juebner, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Beike, Justus UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothschild, Markus A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bender, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-492858
DOI:	10.1007/s00216-010-4171-0
Journal or Publication Title:	Anal. Bioanal. Chem.
Volume:	398
Number:	5
Page Range:	S. 2141 - 2154
Date:	2010
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1618-2650
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANNABINOID RECEPTOR CB2; ACTIVATION; IDENTIFICATION; INHIBITION; INDOLES; GROWTH; VIVO Multiple languages Biochemical Research Methods; Chemistry, Analytical Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49285