Metabolic profile of mephedrone: identification of nor-mephedrone conjugates with dicarboxylic acids as a new type of xenobiotic phase II metabolites

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F16%3A43914802" target="_blank" >RIV/00023752:_____/16:43914802 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/16:10318098 RIV/60461373:22310/16:43902188

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0378427415300916" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0378427415300916</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.toxlet.2015.10.025" target="_blank" >10.1016/j.toxlet.2015.10.025</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Metabolic profile of mephedrone: identification of nor-mephedrone conjugates with dicarboxylic acids as a new type of xenobiotic phase II metabolites

Popis výsledku v původním jazyce

Metabolic profile of mephedrone (4-methylmethcathinone, 4-MMC), a frequently abused recreational drug, was determined in rats in vivo. The urine of rats dosed with a subcutaneous bolus dose of 20 mg 4-MMC/kg was analysed by LC/MS. Ten phase I and five phase II metabolites were identified by comparison of their retention times and MS2 spectra with those of authentic reference standards and/or with the MS2 spectra of previously identified metabolites. The main metabolic pathway was N-demethylation leading to normephedrone (4-methylcathinone, 4-MC) which was further conjugated with succinic, glutaric and adipic acid. Other phase I metabolic pathways included oxidation of the 4-methyl group, carbonyl reduction leading to dihydro-metabolites and -oxidation at the position 3'. Five of the metabolites detected, namely, 4-carboxynormephedrone (4-carboxycathinone, 4-CC), 4-carboxydihydronormephedrone (4-carboxynorephedrine, 4-CNE), hydroxytolyldihydronormephedrone (4-hydroxymethylnorephedrine, 4-OH-MNE) and conjugates of 4-MC with glutaric and adipic acid, have not been reported as yet. The last two conjugates represent a novel, hitherto unexploited, type of phase II metabolites in mammals together with an analogous succinic acid conjugate of 4-MC identified by Pozo et al. (2015). These conjugates might be potentially of great importance in the metabolism of other psychoactive amines.

Název v anglickém jazyce

Metabolic profile of mephedrone: identification of nor-mephedrone conjugates with dicarboxylic acids as a new type of xenobiotic phase II metabolites

Popis výsledku anglicky

Metabolic profile of mephedrone (4-methylmethcathinone, 4-MMC), a frequently abused recreational drug, was determined in rats in vivo. The urine of rats dosed with a subcutaneous bolus dose of 20 mg 4-MMC/kg was analysed by LC/MS. Ten phase I and five phase II metabolites were identified by comparison of their retention times and MS2 spectra with those of authentic reference standards and/or with the MS2 spectra of previously identified metabolites. The main metabolic pathway was N-demethylation leading to normephedrone (4-methylcathinone, 4-MC) which was further conjugated with succinic, glutaric and adipic acid. Other phase I metabolic pathways included oxidation of the 4-methyl group, carbonyl reduction leading to dihydro-metabolites and -oxidation at the position 3'. Five of the metabolites detected, namely, 4-carboxynormephedrone (4-carboxycathinone, 4-CC), 4-carboxydihydronormephedrone (4-carboxynorephedrine, 4-CNE), hydroxytolyldihydronormephedrone (4-hydroxymethylnorephedrine, 4-OH-MNE) and conjugates of 4-MC with glutaric and adipic acid, have not been reported as yet. The last two conjugates represent a novel, hitherto unexploited, type of phase II metabolites in mammals together with an analogous succinic acid conjugate of 4-MC identified by Pozo et al. (2015). These conjugates might be potentially of great importance in the metabolism of other psychoactive amines.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/VG20122015075" target="_blank" >VG20122015075: Nové syntetické drogy (NSD) - vytvoření komplexní toxikologické databáze, vývoj metodik jejich detekce včetně rychlých imunochemických testů, jejich behaviorální farmakologie, farmakokinetika a biotransformace u potkanů, epidemiologie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Toxicology Letters

ISSN

0378-4274

e-ISSN

—

Svazek periodika

240

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

8

Strana od-do

114-121

Kód UT WoS článku

000367538300012

EID výsledku v databázi Scopus

2-s2.0-84946599647