ArticleBritish journal of pharmacology2013
Real-time characterization of cannabinoid receptor 1 (CB1 ) allosteric modulators reveals novel mechanism of action.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 115 citations in OpenAlex.
- Transcriptional Mapping of the Human Cannabinoid Receptor 1 (Molecules (Basel, Switzerland) · 2026Article
- AB-MDMSBA-Not a Synthetic Cannabinoid Receptor Agonist.Pharmacology research & perspectives · 2026Article
- Leveraging machine learning for selective cannabinoid ligand discovery: methods, challenges, and opportunities.Expert opinion on drug discovery · 2026Review
- Insights into cannabinoid receptor 2 (CB2) anterograde trafficking and pharmacological chaperoning.Cellular and molecular life sciences : CMLS · 2025Article
- Effects of CB1 receptor negative allosteric modulator Org27569 on oxycodone withdrawal symptoms in mice.Psychopharmacology · 2024Article
- Negative allosteric modulation of CB1 cannabinoid receptor signalling decreases intravenous morphine self-administration and relapse in mice.Addiction biology · 2024Article
- Insight into the mechanism of action of ORG27569 at the cannabinoid type one receptor utilising a unified mathematical model.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The CB1 negative allosteric modulator PSNCBAM-1 reduces ethanol self-administration via a nonspecific hypophagic effect.Pharmacology, biochemistry, and behavior · 2024Article
- Pharmacological evaluation of new generation OXIZID synthetic cannabinoid receptor agonists.European journal of pharmacology · 2024Article
- Novel Cannabinoid Receptor 2 (CB2) Low Lipophilicity Agonists Produce Distinct cAMP and Arrestin Signalling Kinetics without Bias.International journal of molecular sciences · 2023Article
- The piperazine analogue para-fluorophenylpiperazine alters timing of the physiological effects of the synthetic cannabinoid receptor agonist AMB-FUBINACA, without changing its discriminative stimulus, signalling effects, or metabolism.Pharmacology, biochemistry, and behavior · 2023Article
- Article
- Characterisation of AMB-FUBINACA metabolism and CBForensic toxicology · 2023Article
- In Vitro Characterization of 6-Methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1ACS pharmacology & translational science · 2022Article
- Exploring determinants of agonist efficacy at the CB1 cannabinoid receptor: Analogues of the synthetic cannabinoid receptor agonist EG-018.Pharmacology research & perspectives · 2022Article
- Development of 3-(4-Chlorophenyl)-1-(phenethyl)urea Analogues as Allosteric Modulators of the Cannabinoid Type-1 Receptor: RTICBM-189 is Brain Penetrant and Attenuates Reinstatement of Cocaine-Seeking Behavior.Journal of medicinal chemistry · 2022Article
- CB1 Cannabinoid Receptor Signaling and Biased Signaling.Molecules (Basel, Switzerland) · 2021Review
- Rational design of cannabinoid type-1 receptor allosteric modulators: Org27569 and PSNCBAM-1 hybrids.Bioorganic & medicinal chemistry · 2021Article
- Assessment of select synthetic cannabinoid receptor agonist bias and selectivity between the type 1 and type 2 cannabinoid receptor.Scientific reports · 2021Article
- Molecular Pharmacology of Synthetic Cannabinoids: Delineating CB1 Receptor-Mediated Cell Signaling.International journal of molecular sciences · 2020Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe cannabinoid receptor type 1 (CB1 ) has an allosteric binding site. The drugs ORG27569 {5-chloro-3-ethyl-N-[2-[4-(1-piperidinyl)phenyl]ethyl]-1H-indole-2-carboxamide} and PSNCBAM-1 {1-(4-chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea} have been extensively characterized with regard to their effects on signalling of the orthosteric ligand CP55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol}, and studies have suggested that these allosteric modulators increase binding affinity but act as non-competitive antagonists in functional assays. To gain a deeper understanding of allosteric modulation of CB1 , we examined real-time signalling and trafficking responses of the receptor in the presence of allosteric modulators. EXPERIMENTAL APPROACH: Studies of CB1 signalling were carried out in HEK 293 and AtT20 cells expressing haemagglutinin-tagged human and rat CB1 . We measured real-time accumulation of cAMP, activation and desensitization of potassium channel-mediated cellular hyperpolarization and CB1 internalization. KEY
resultsORG27569 and PSNCBAM-1 produce a complex, concentration and time-dependent modulation of agonist-mediated regulation of cAMP levels, as well as an increased rate of desensitization of CB1 -mediated cellular hyperpolarization and a decrease in agonist-induced receptor internalization. CONCLUSIONS AND IMPLICATIONS: Contrary to previous studies characterizing allosteric modulators at CB1, this study suggests that the mechanism of action is not non-competitive antagonism of signalling, but rather that enhanced binding results in an increased rate of receptor desensitization and reduced internalization, which results in time-dependent modulation of cAMP signalling. The observed effect of the allosteric modulators is therefore dependent on the time frame over which the signalling response occurs. This finding may have important consequences for the potential therapeutic application of these compounds.
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