Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60193697%3A_____%2F17%3AN0000039" target="_blank" >RIV/60193697:_____/17:N0000039 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/17:10361099 RIV/60461373:22310/17:43913321 RIV/00023752:_____/17:43915067

Výsledek na webu

<a href="http://dx.doi.org/10.1080/00498254.2016.1199919" target="_blank" >http://dx.doi.org/10.1080/00498254.2016.1199919</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/00498254.2016.1199919" target="_blank" >10.1080/00498254.2016.1199919</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites

Popis výsledku v původním jazyce

5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards.

Název v anglickém jazyce

Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites

Popis výsledku anglicky

5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

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

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

XENOBIOTICA

ISSN

0049-8254

e-ISSN

1366-5928

Svazek periodika

47

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

505-514

Kód UT WoS článku

000399917500006

EID výsledku v databázi Scopus

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