In vitro phase I metabolism of the synthetic cannabimimetic JWH-018

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschung

Standard

In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. / Wintermeyer, Annette; Möller, Ines; Thevis, Mario; Jübner, Martin; Beike, Justus; Rothschild, Markus A; Bender, Katja.

in: Analytical and bioanalytical chemistry, Jahrgang 398, Nr. 5, 01.11.2010, S. 2141-2153.

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschung

Harvard

Wintermeyer, A, Möller, I, Thevis, M, Jübner, M, Beike, J, Rothschild, MA & Bender, K 2010, 'In vitro phase I metabolism of the synthetic cannabimimetic JWH-018', Analytical and bioanalytical chemistry, Jg. 398, Nr. 5, S. 2141-2153. https://doi.org/10.1007/s00216-010-4171-0

APA

Wintermeyer, A., Möller, I., Thevis, M., Jübner, M., Beike, J., Rothschild, M. A., & Bender, K. (2010). In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. Analytical and bioanalytical chemistry, 398(5), 2141-2153. https://doi.org/10.1007/s00216-010-4171-0

Vancouver

Bibtex

@article{e92fdf7a732d4ab5bafbeec4698cae08,
title = "In vitro phase I metabolism of the synthetic cannabimimetic JWH-018",
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.",
keywords = "Chromatography, High Pressure Liquid, Humans, Indoles, Mass Spectrometry, Microsomes, Liver, Models, Biological, Naphthalenes, Receptor, Cannabinoid, CB1",
author = "Annette Wintermeyer and Ines M{\"o}ller and Mario Thevis and Martin J{\"u}bner and Justus Beike and Rothschild, {Markus A} and Katja Bender",
year = "2010",
month = nov,
day = "1",
doi = "10.1007/s00216-010-4171-0",
language = "English",
volume = "398",
pages = "2141--2153",
journal = "Analytical and bioanalytical chemistry",
issn = "1618-2642",
publisher = "Springer Verlag",
number = "5",

}

RIS

TY - JOUR

T1 - In vitro phase I metabolism of the synthetic cannabimimetic JWH-018

AU - Wintermeyer, Annette

AU - Möller, Ines

AU - Thevis, Mario

AU - Jübner, Martin

AU - Beike, Justus

AU - Rothschild, Markus A

AU - Bender, Katja

PY - 2010/11/1

Y1 - 2010/11/1

N2 - 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.

AB - 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.

KW - Chromatography, High Pressure Liquid

KW - Humans

KW - Indoles

KW - Mass Spectrometry

KW - Microsomes, Liver

KW - Models, Biological

KW - Naphthalenes

KW - Receptor, Cannabinoid, CB1

U2 - 10.1007/s00216-010-4171-0

DO - 10.1007/s00216-010-4171-0

M3 - Journal articles

C2 - 20838779

VL - 398

SP - 2141

EP - 2153

JO - Analytical and bioanalytical chemistry

JF - Analytical and bioanalytical chemistry

SN - 1618-2642

IS - 5

ER -

ID: 131453