Identification of a Novel Cannabimimetic Phenylacetylindole, Cannabipiperidiethanone, as a Designer Drug in a Herbal Product and Its Affinity for Cannabinoid CB1 and CB2 Receptors

Uchiyama, Nahoko; Kikura‐Hanajiri, Ruri; Goda, Yukihiro

doi:10.1248/cpb.59.1203

Cited by 56 publications

(35 citation statements)

References 13 publications

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“…Synthetic cannabinoids, a group of substances with generally similar chemical structures binding to the cannabinoid receptor type 1 (CB 1 ) or type 2 (CB 2 ), were first identified in Bherbal mixtures^in 2008 [1][2][3]. Structure-activity relationships for synthetic cannabinoids have been established [4][5][6][7][8], and JWH compounds (JWH-018, JWH-122, and JWH-073) have been modified as follows: introduction of a fluorine atom (AM-2201, MAM-2201, and EAM-2201) [9] and substitution of the naphthyl group for a cyclopropyl group (UR-144 and XLR-11) [10,11], adamantyl group (APICA and 5F-APICA) [10], or quinolinyl group (QUPIC and QUCHIC) [12,13].…”

Section: Introductionmentioning

confidence: 99%

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

et al. 2016

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MAM-2201 is a synthetic cannabinoid that is increasingly found in recreational drug abusers and cases of severe intoxication. Thus, characterization of the metabolic pathways of MAM-2201 is necessary to predict individual pharmacokinetics and toxicity differences, and to avoid toxic drug-drug interactions. Collectively, 19 phase 1 metabolites of MAM-2201 were identified using liquid chromatography-Orbitrap mass spectrometry following human liver microsomal incubations in the presence of NADPH: 7 hydroxy-MAM-2201 (M1-M7), 4 dihydroxy-MAM-2201 (M8-M11), dihydrodiol-MAM-2201 (M12), N-(5-hydroxypentyl)-MAM-2201 (M13), hydroxy-M13 (M14), N-dealkyl-MAM-2201 (M15), 2 hydroxy-M15 (M16, M17), MAM-2201 N-pentanoic acid (M18), and hydroxy-M18 (M19). On the basis of intrinsic clearance values in human liver microsomes, hydroxy-MAM-2201 (M1), N-(5-hydroxypentyl)-MAM-2201 (M13), and hydroxy-M13 (M14) were the major metabolites. Based on an enzyme kinetics study using human cDNA-expressed cytochrome P450 (CYP) enzymes and an immunoinhibition study using selective CYP antibodies in human liver microsomes, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 enzymes were responsible for MAM-2201 metabolism. The CYP3A4 enzyme played a prominent role in MAM-2201 metabolism, and CYP1A2, CYP2B6, CYP2C8, and CYP2C9 enzymes played major roles in the formation of some metabolites. MAM-2201 is extensively metabolized by multiple CYP enzymes, indicating that MAM-2201 and its metabolites should be used as markers of MAM-2201 abuse and toxicity. Graphical abstract In vitro metabolic pathways of MAM-2201 were characterized in human liver microsomes and recombinant CYPs using LC-HRMS analysis. Total 19 phase I metabolites were identified with predominant contribution of CYP3A4.

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Section: Introductionmentioning

confidence: 99%

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

et al. 2016

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“…Recently, previously uncharacterized chemicals have been discovered suggesting that the chemists responsible for this market have begun to create entirely new compounds (Jankovics, Varadi, Tolgyesi, Lohner, Nemeth-Palotas, & Balla, 2012; Simolka, Lindigkeit, Schiebel, Papke, Ernst, & Beuerle, 2012; Uchiyama, Kikura-Hanajiri, & Goda, 2011). …”

Section: Synthetic Cannabinoidsmentioning

confidence: 99%

Novel Drugs of Abuse: A Snapshot of an Evolving Marketplace

Vandrey¹,

Johnson²,

Johnson³

et al. 2013

APS

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Background & objectives-Over the past decade, non-medical use of novel drugs has proliferated worldwide. In most cases these are synthetic drugs first synthesized in academic or pharmaceutical laboratories for research or drug development purposes, but also include naturally occurring substances that do not fit the typical pharmacological or behavioral profile of traditional illicit substances. Perhaps most unique to this generation of new drugs is that they are being sold over the counter and on the Internet as "legal highs" or substitutes for traditional illicit drugs such as cannabis, cocaine, amphetamines, MDMA, and LSD. The purpose of this review is to provide an overview of novel drugs in current use, including the epidemiology of use and toxicologic and pharmacological properties, and to offer some guidelines to clinicians who see patients experiencing adverse effects from these drugs.

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“…These mixtures were sold under a wide variety of names, including 'Spice', 'Yucatan Fire', 'Smoke', 'Sence', 'Skunk', 'Space', 'K2 , 'K2 Citron', 'K2 Blonde', 'K2 Strawberry', 'K2 Pink', 'K3 , and 'K4 . Many such products were reportedly adulterated with synthetic cannabinoids with varying degrees of selectivity and affinity for cannabinoid CB1 and CB2 receptors [1][2][3]. As most of the products have potentially psychotropic effects, these compounds were also banned in many European countries since 2009 [4].…”

Section: Introductionmentioning

confidence: 99%

Study on the mass fragmentation pathway of the synthetic cannabinoids JWH-018 and JWH-073

Xing

Liu

et al. 2015

International Journal of Mass Spectrometry

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Identification of a Novel Cannabimimetic Phenylacetylindole, Cannabipiperidiethanone, as a Designer Drug in a Herbal Product and Its Affinity for Cannabinoid CB1 and CB2 Receptors

Cited by 56 publications

References 13 publications

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

Novel Drugs of Abuse: A Snapshot of an Evolving Marketplace

Study on the mass fragmentation pathway of the synthetic cannabinoids JWH-018 and JWH-073

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