| Reference | 1. Drug Test Anal. 2017 Aug 18. doi: 10.1002/dta.2262. [Epub ahead of print]
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Kinetic and metabolic profiles of synthetic cannabinoids NNEI and MN-18.
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Kevin RC(1)(2), Lefever TW(3), Snyder RW(3), Patel PR(3), Gamage TF(3), Fennell
TR(3), Wiley JL(3), McGregor IS(1)(2), Thomas BF(3).
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Author information: <br>
(1)School of Psychology, The University of Sydney, NSW, Australia.
(2)The Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney,
NSW, Australia.
(3)RTI International, NC, USA.
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In 2014 and 2015, synthetic cannabinoid receptor agonists NNEI
(N-1-naphthalenyl-1-pentyl-1H-indole-3-carboxamide) and MN-18
(N-1-naphthalenyl-1-pentyl-1H-indazole-3-carboxamide) were detected in
recreationally used and abused products in multiple countries, and were
implicated in episodes of poisoning and toxicity. Despite this, the
pharmacokinetic profiles of NNEI and MN-18 have not been characterized. In the
present study NNEI and MN-18 were incubated in rat and human liver microsomes and
hepatocytes, to estimate kinetic parameters and to identify potential metabolic
pathways, respectively. These parameters and pathways were then examined in vivo,
via analysis of blood and urine samples from catheterized male rats following
intraperitoneal (3 mg/kg) administration of NNEI and MN-18. Both NNEI and MN-18
were rapidly cleared by rat and human liver microsomes, and underwent a range of
oxidative transformations during incubation with rat and human hepatocytes.
Several unique metabolites were identified for the forensic identification of
NNEI and MN-18 intake. Interestingly, NNEI underwent a greater number of
biotransformations (20 NNEI metabolites versus 10 MN-18 metabolites), yet parent
MN-18 was eliminated at a faster rate than NNEI in vivo. Additionally, in vivo
elimination was more rapid than in vitro estimates. These data highlight that
even closely related synthetic cannabinoids can possess markedly distinct
pharmacokinetic profiles, which can vary substantially between in vitro and in
vivo models.
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2. Forensic Toxicol. 2015;33(2):244-259. Epub 2015 Feb 11.
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A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic
cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine
derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly
identified in illegal products.
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Uchiyama N(1), Shimokawa Y(1), Kikura-Hanajiri R(1), Demizu Y(1), Goda Y(1),
Hakamatsuka T(1).
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Author information: <br>
(1)Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of
Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501 Japan.
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Six new psychoactive substances were identified together with two other
substances (compounds 1-8) in illegal products by our ongoing survey in Japan
between January and July 2014. A new synthetic cannabinoid, FDU-NNEI
[1-(4-fluorobenzyl)-N-(naphthalen-1-yl)-1H-indole-3-carboxamide, 2], was detected
with the newly distributed synthetic cannabinoid FDU-PB-22 (1). Two 2H-indazole
isomers of synthetic cannabinoids, AB-CHMINACA 2H-indazole analog (3) and NNEI
2H-indazole analog (4), were newly identified with 1H-indazoles [AB-CHMINACA and
NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N-(naphthalen-1-yl)
carbamate (5) and isobutyl 1-pentyl-1H-indazole-3-carboxylate (6) were detected
in illegal products. Compound 6 is considered to be a by-product of the
preparation of NNEI indazole analog from compound 5 and 1-pentyl-1H-indazole. A
phenethylamine derivative, N-OH-EDMA<br>
[N-hydroxy-3,4-ethylenedioxy-N-methylamphetamine, 7], and a cathinone derivative,
dimethoxy-α-PHP (dimethoxy-α-pyrrolidinohexanophenone, 8), were newly identified
in illegal products. Among them, compounds 1 and 8 have been controlled as
designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in
Japan since August and November 2014, respectively.
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