scholarly journals Metabolism, CB1 cannabinoid receptor binding and in vivo activity of synthetic cannabinoid 5F-AKB48: Implications for toxicity

2020 ◽  
Vol 195 ◽  
pp. 172949 ◽  
Author(s):  
Anna Pinson ◽  
Azure L. Yarbrough ◽  
John M. Bush ◽  
Christian V. Cabanlong ◽  
Amal Shoeib ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
Cb1 Cannabinoid Receptor

scholarly journals GPR18, GPR55 and GPR119 (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Stephen P.H. Alexander ◽  
Andrew J. Irving
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Structural Similarity ◽  
Synthetic Cannabinoid ◽  
Receptor Ligands ◽  
Orphan Status ◽  
Endogenous Cannabinoid

GPR18, GPR55 and GPR119 (provisional nomenclature), although showing little structural similarity to CB1 and CB2 cannabinoid receptors, respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [98]. Although there are multiple reports to indicate that GPR18, GPR55 and GPR119 can be activated in vitro by N-arachidonoylglycine, lysophosphatidylinositol and N-oleoylethanolamide, respectively, there is a lack of evidence for activation by these lipid messengers in vivo. As such, therefore, these receptors retain their orphan status.

scholarly journals In vitro and in vivo pharmacological evaluation of the synthetic cannabinoid receptor agonist EG-018

2020 ◽  
Vol 193 ◽  
pp. 172918
Author(s):  
Thomas F. Gamage ◽  
Daniel G. Barrus ◽  
Richard C. Kevin ◽  
David B. Finlay ◽  
Timothy W. Lefever ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
Pharmacological Evaluation ◽  
Synthetic Cannabinoid Receptor Agonist

scholarly journals Assessment of select synthetic cannabinoid receptor agonist bias and selectivity between the type 1 and type 2 cannabinoid receptor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ayat Zagzoog ◽  
Asher L. Brandt ◽  
Tallan Black ◽  
Eunhyun D. Kim ◽  
Riley Burkart ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Partial Agonist ◽  
Synthetic Cannabinoid ◽  
Receptor Subtype ◽  
Service Agency ◽  
Subtype Selectivity ◽  
Insight Into

AbstractThe first synthetic cannabinoid receptor agonists (SCRAs) were designed as tool compounds to study the endocannabinoid system’s two predominant cannabinoid receptors, CB1R and CB2R. Unfortunately, novel SCRAs now represent the most rapidly proliferating novel psychoactive substances (NPS) of abuse globally. Unlike ∆9-tetrahydrocannabinol, the CB1R and CB2R partial agonist and the intoxicating constituent of Cannabis, many SCRAs characterized to date are full agonists of CB1R. Gaining additional insight into the pharmacological activity of these SCRAs is critical to assess and regulate NPSs as they enter the marketplace. The purpose of this study was to assess select SCRAs recently identified by Canadian police, border service agency, private companies and the illicit market as potential CB1R and CB2R agonists. To this end, fifteen SCRAs were screened for in vitro activity and in silico interactions at CB1R and CB2R. Several SCRAs were identified as being highly biased for cAMP inhibition or βarrestin2 recruitment and receptor subtype selectivity between CB1R and CB2R. The indazole ring and halogen-substituted butyl or pentyl moieties were identified as two structural features that may direct βarrestin2 bias. Two highly-biased SCRAs—JWH-018 2′-napthyl-N-(3-methylbutyl) isomer (biased toward cAMP inhibition) and 4-fluoro MDMB-BINACA (biased toward βarrestin2 recruitment) displayed unique and differential in vivo activity in mice. These data provide initial insight into the correlations between structure, signalling bias, and in vivo activity of the SCRAs.

scholarly journals Synthetic Cannabinoid Agonist WIN 55212-2 Targets Proliferation, Angiogenesis, and Apoptosis via MAPK/AKT Signaling in Human Endometriotic Cell Lines and a Murine Model of Endometriosis

2021 ◽  
Vol 3 ◽  
Author(s):  
Harshavardhan Lingegowda ◽  
Jessica E. Miller ◽  
Ryan M. Marks ◽  
Lindsey K. Symons ◽  
Taylor Alward ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
Self Medication ◽  
Syngeneic Mouse ◽  
Win 55 ◽  
Pain Stimuli ◽  
Potential Therapeutic Intervention

Endometriosis (EM) is characterized by the growth of endometrium-like tissue outside the uterus, leading to chronic inflammation and pelvic pain. Lesion proliferation, vascularization, and associated inflammation are the hallmark features of EM lesions. The legalization of recreational cannabinoids has garnered interest in the patient community and is contributing to a greater incidence of self medication; however, it remains unknown if cannabinoids possess marked disease-modifying properties. In this study, we assess the effects of synthetic cannabinoid, WIN 55212-2 (WIN 55), in EM-representative in vitro and in vivo syngeneic mouse models. WIN 55 reduced proliferation and angiogenesis in vitro, via MAPK/Akt-mediated apoptosis. These findings were corroborated in a mouse model of EM, where we found reduced TRPV1 expression in the dorsal root ganglia of the EM mouse model exposed to WIN 55, suggesting reduced signaling of pain stimuli. Ultimately, these pieces of evidence support the use of cannabinoid receptor agonists as a potential therapeutic intervention for EM associated pain and inflammation.

An in vivo [18F]MK-9470 microPET study of type 1 cannabinoid receptor binding in Wistar rats after chronic administration of valproate and levetiracetam

2008 ◽  
Vol 54 (7) ◽  
pp. 1103-1106 ◽  
Author(s):  
Karolien Goffin ◽  
Guy Bormans ◽  
Cindy Casteels ◽  
Barbara Bosier ◽  
Didier M. Lambert ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Wistar Rats ◽  
Cannabinoid Receptor ◽  
Chronic Administration ◽  
Type 1 Cannabinoid Receptor

scholarly journals N-acyl-dopamines: novel synthetic CB1 cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo

2000 ◽  
Vol 351 (3) ◽  
pp. 817 ◽  
Author(s):  
Tiziana BISOGNO ◽  
Dominique MELCK ◽  
Mikhail Yu. BOBROV ◽  
Natalia M. GRETSKAYA ◽  
Vladimir V. BEZUGLOV ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Ligands ◽  
Cb1 Cannabinoid Receptor

scholarly journals A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1396
Author(s):  
Andrew M. Brandon ◽  
Lysbeth H. Antonides ◽  
Jennifer Riley ◽  
Ola Epemolu ◽  
Denise A. McKeown ◽  
...  
Keyword(s):  
Illicit Drug ◽  
Cannabinoid Receptor ◽  
Liver Microsomes ◽  
Drug Market ◽  
Synthetic Cannabinoid ◽  
Pharmacokinetic Studies ◽  
Receptor Agonists ◽  
Synthetic Cannabinoid Receptor Agonists

In vitro pharmacokinetic studies were conducted on enantiomer pairs of twelve valinate or tert-leucinate indole and indazole-3-carboxamide synthetic cannabinoid receptor agonists (SCRAs) detected on the illicit drug market to investigate their physicochemical parameters and structure-metabolism relationships (SMRs). Experimentally derived Log D7.4 ranged from 2.81 (AB-FUBINACA) to 4.95 (MDMB-4en-PINACA) and all SCRAs tested were highly protein bound, ranging from 88.9 ± 0.49% ((R)-4F-MDMB-BINACA) to 99.5 ± 0.08% ((S)-MDMB-FUBINACA). Most tested SCRAs were cleared rapidly in vitro in pooled human liver microsomes (pHLM) and pooled cryopreserved human hepatocytes (pHHeps). Intrinsic clearance (CLint) ranged from 13.7 ± 4.06 ((R)-AB-FUBINACA) to 2944 ± 95.9 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHLM, and from 110 ± 34.5 ((S)-AB-FUBINACA) to 3216 ± 607 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHHeps. Predicted Human in vivo hepatic clearance (CLH) ranged from 0.34 ± 0.09 ((S)-AB-FUBINACA) to 17.79 ± 0.20 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHLM and 1.39 ± 0.27 ((S)-MDMB-FUBINACA) to 18.25 ± 0.12 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHHeps. Valinate and tert-leucinate indole and indazole-3-carboxamide SCRAs are often rapidly metabolised in vitro but are highly protein bound in vivo and therefore predicted in vivo CLH is much slower than CLint. This is likely to give rise to longer detection windows of these substances and their metabolites in urine, possibly as a result of accumulation of parent drug in lipid-rich tissues, with redistribution into the circulatory system and subsequent metabolism.

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