Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS

@article{Zhang2006IdentificationOI,
  title={Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS},
  author={Qiang Zhang and Peng Ma and Richard B. Cole and Guangdi Wang},
  journal={Analytical and Bioanalytical Chemistry},
  year={2006},
  volume={386},
  pages={1345-1355}
}
The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high binding affinity at the peripheral cannabinoid receptor CB2, has been studied. A total of 22 metabolites were identified and structurally characterized. The metabolites are products of: 1) monohydroxylation on the naphthalene ring (m/z 344, M20 and M21), indole ring (m/z 344, M17 and M18), or the N-alkyl group (m/z 344, M14); 2) arene oxidation leading to dihydrodiols (m/z 362, M12 and M15); 3) dihydroxylation on the… 
In vitro phase I metabolism of the synthetic cannabimimetic JWH-018
TLDR
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, and evidence of trihydroxylation at different locations of the hydroxyl groups in the molecule was found.
Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity
TLDR
This study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R), and suggests that metabolites of most drugs, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs.
In vitro and in vivo metabolisms of 1-pentyl-3-(4-methyl-1-naphthoyl)indole (JWH-122)
TLDR
It was concluded that all metabolites formed in vivo were excreted conjugated as glucuronide or sulfate, with conjugation rates above 50 %.
In vitro metabolism of indomethacin morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB(2)) in rat liver microsomes.
Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism.
TLDR
It is suggested that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples, and the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from Jwh-018 use.
Conjugation of Synthetic Cannabinoids JWH-018 and JWH-073, Metabolites by Human UDP-Glucuronosyltransferases
TLDR
Nine human recombinant uridine diphosphate-glucuronosyltransferase (UGT) isoforms and human liver and intestinal microsomes are evaluated for their ability to glucuronidate hydroxylated metabolites of K2, which indicates that K2 metabolites may be rapidly glucuronidated and eliminated from the body.
Chromatography-mass spectrometry studies on the metabolism of synthetic cannabinoids JWH-018 and JWH-073, psychoactive components of smoking mixtures.
Application of mass spectrometry to the structural identification of the metabolites of the synthetic cannabinoid JWH-018 and the determination of them in human urine
TLDR
The urinary metabolites of 1-pentyl-3-(1-naphthoyl)indole (JWH-018) and a procedure for determining them in urine are reported and the structure of minor metabolites was proposed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 17 REFERENCES
Characterization of rat liver microsomal metabolites of AM-630, a potent cannabinoid receptor antagonist, by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
TLDR
The in vitro metabolism of AM-630 was studied by high-performance liquid chromatography coupled with tandem mass spectrometry and found that it behaves primarily as a potent CB2-selective antagonist.
In vitro metabolism of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate, a cannabinoid receptor agonist.
TLDR
In this study, in vitro metabolism of WIN55212-2 in rat liver microsome was investigated and two major metabolites have been isolated in pure form, allowing future receptor binding studies to be conducted.
IN VITRO METABOLISM OF DIARYLPYRAZOLES, A NOVEL GROUP OF CANNABINOID RECEPTOR LIGANDS
TLDR
A study of the in vitro metabolisms of three diarylpyrazole analogs, SR141716A, AM251, and AM281, in rat liver microsomes, using high-performance liquid chromatography with UV and mass spectrometry detectors finds all identified metabolites are characterized by structural modifications on the terminal group of the 3-substituent.
Molecular characterization of a peripheral receptor for cannabinoids
TLDR
The cloning of a receptor for cannabinoids is reported that is not expressed in the brain but rather in macrophages in the marginal zone of spleen, which helps clarify the non-psychoactive effects of cannabinoids.
Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1).
TLDR
ACPA and ACEA are high-affinity agonists of the CB1 receptor but do not bind the CB2 receptor, suggesting that structural analogs of AEA can be designed with considerable selectivity for theCB1 receptor over theCB2 receptor.
SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor.
TLDR
It is expected that SR 144528 will provide a powerful tool to investigate the in vivo functions of the cannabinoid system in the immune response.
Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands.
TLDR
Although most of the chosen compounds did not discriminate between CB1 and CB2, several ligands were identified that showed selectivity and can now serve as a basis for the design of compounds with even greater selectivity.
Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors.
TLDR
Except for its inability to couple to the modulation of Q-type calcium channels or inwardly rectifying potassium channels, the CB1 and CB2 receptors display similar pharmacological and biochemical properties.
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
TLDR
The cloning and expression of a complementary DNA that encodes a G protein-coupled receptor that is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana are suggested.
...
1
2
...