ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 173 citations in OpenAlex.
- Cannabinoid CBBritish journal of pharmacology · 2026Article
- Sex-specific differences in endocannabinoid regulation of cocaine-evoked dopamine in the medial nucleus accumbens shell.bioRxiv : the preprint server for biology · 2026Article
- SU-Eohyeol Pharmacopuncture Ameliorates Parkinson's Disease-Associated Pain via the CB1 and PPARγ Pathways in an MPTP-Induced Mouse Model.Pain research & management · 2026Article
- Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026Review
- Structural Perspectives on Biased Allostery of GPCR Signaling.Handbook of experimental pharmacology · 2026Review
- An orally bioavailable MrgprX1-positive allosteric modulator alleviates certain neuropathic pain-related behaviors in humanized mice.Science translational medicine · 2025Article
- Allosteric Modulation of Cannabinoid Type 1 Receptor by ZCZ011: Integration of In Vitro Pharmacology and Molecular Dynamics Simulation.ACS bio & med chem Au · 2025Article
- Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery.Acta pharmacologica Sinica · 2025Review
- Accurate Tracking of Locomotory Kinematics in Mice Moving Freely in Three-Dimensional Environments.eNeuro · 2025Article
- The synthetic cannabinoid agonist WIN 55,212-2 reduces experimental pruritus via CBNeuropharmacology · 2025Article
- Identification of a Cannabinoid Receptor 2 Allosteric Site Using Computational Modeling and Pharmacological Analysis.ACS pharmacology & translational science · 2025Article
- Enhancing Tetrahydrocannabinol's Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pharmacological potential of endocannabinoid and endocannabinoid-like compounds in protecting intestinal structure and metabolism under high-fat conditions.Frontiers in pharmacology · 2025Review
- Structure-based identification of a G protein-biased allosteric modulator of cannabinoid receptor CB1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Investigation of Cannabidiol in the Mouse Drug Discrimination Paradigm.Cannabis and cannabinoid research · 2024Article
- Determination of the Cannabinoid CB1 Receptor's Positive Allosteric Modulator Binding Site through Mutagenesis Studies.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Review
- The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.Psychological medicine · 2023Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
The CB1 receptor represents a promising target for the treatment of several disorders including pain-related disease states. However, therapeutic applications of Δ(9)-tetrahydrocannabinol and other CB1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB1 receptor function for therapeutic gain with the promise of reduced side effects. Here we describe the development of the novel synthetic CB1 PAM, 6-methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1H-indole (ZCZ011), which augments the in vitro and in vivo pharmacological actions of the CB1 orthosteric agonists CP55,940 and N-arachidonoylethanolamine (AEA). ZCZ011 potentiated binding of [(3)H]CP55,940 to the CB1 receptor as well as enhancing AEA-stimulated [(35)S]GTPγS binding in mouse brain membranes and β-arrestin recruitment and ERK phosphorylation in hCB1 cells. In the whole animal, ZCZ011 is brain penetrant, increased the potency of these orthosteric agonists in mouse behavioral assays indicative of cannabimimetic activity, including antinociception, hypothermia, catalepsy, locomotor activity, and in the drug discrimination paradigm. Administration of ZCZ011 alone was devoid of activity in these assays and did not produce a conditioned place preference or aversion, but elicited CB1 receptor-mediated antinociceptive effects in the chronic constriction nerve injury model of neuropathic pain and carrageenan model of inflammatory pain. These data suggest that ZCZ011 acts as a CB1 PAM and provide the first proof of principle that CB1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.