Journal ArticleDOI
CB1 allosteric modulators and their therapeutic potential in CNS disorders.
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TLDR
This review will summarize and critically analyze both the in vitro characterization and in vivo validation of CB1 allosteric modulators developed to date, with a focus on CNS therapeutic effects.Abstract:
CB1 is the most abundant GPCR found in the mammalian brain. It has garnered considerable attention as a potential therapeutic drug target. CB1 is involved in a wide range of physiological and psychiatric processes and has the potential to be targeted in a wide range of disease states. However, most of the selective and non-selective synthetic CB1 agonists and antagonists/inverse agonists developed to date are primarily used as research tools. No novel synthetic cannabinoids are currently in the clinic for use in psychiatric illness; synthetic analogues of the phytocannabinoid THC are on the market to treat nausea and vomiting caused by cancer chemotherapy, along with off-label use for pain. Novel strategies are being explored to target CB1, but with emphasis on the elimination or mitigation of the potential psychiatric adverse effects that are observed by central agonism/antagonism of CB1. New pharmacological options are being pursued that may avoid these adverse effects while preserving the potential therapeutic benefits of CB1 modulation. Allosteric modulation of CB1 is one such approach. In this review, we will summarize and critically analyze both the in vitro characterization and in vivo validation of CB1 allosteric modulators developed to date, with a focus on CNS therapeutic effects.read more
Citations
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Journal ArticleDOI
The Endocannabinoidome in Neuropsychiatry: Opportunities and Potential Risks.
Gerwyn Morris,Ken Walder,Stefan Kloiber,Stefan Kloiber,Paul Amminger,Michael Berk,Michael Berk,Chiara C. Bortolasci,Michael Maes,Michael Maes,Michael Maes,Basant K. Puri,Andre F. Carvalho +12 more
TL;DR: The endocannabinoid system (ECS) comprises two cognate receptors referred to as CB1R and CB2R as discussed by the authors, which play an essential neuroprotective role by providing a defense against the development of glutamate-mediated excitotoxicity, which is achieved by impeding AMPA-mediated increase in intracellular calcium overload and oxidative stress.
Journal ArticleDOI
Pharmacological selection of cannabinoid receptor effectors: Signalling, allosteric modulation and bias.
TL;DR: The type-1 cannabinoid receptor (CB1) is a promising drug target for a wide range of diseases as discussed by the authors, however, many existing and novel candidate ligands for CB1 have shown only limited therapeutic potential.
Journal ArticleDOI
Effects of the cannabinoid receptor 1 positive allosteric modulator GAT211 and acute MK-801 on visual attention and impulsivity in rats assessed using the five-choice serial reaction time task
Timothy J. Onofrychuk,Shuang Cai,Dan L. McElroy,Andrew J. Roebuck,Quentin Greba,Sumanta Garai,Ganesh A. Thakur,Robert B. Laprairie,John G. Howland +8 more
TL;DR: The dramatic effects of acute MK-801 treatment on behavioral measures of attention and impulsivity are confirmed and continued investigation of CB1R positive allosteric modulators as potential treatments for the cognitive symptoms of schizophrenia and related disorders should be pursued.
Journal ArticleDOI
The Impact of the Secondary Binding Pocket on the Pharmacology of Class A GPCRs
TL;DR: The research group showed that SBP binders contribute significantly to the affinity, selectivity, functional activity, functional selectivity and binding kinetics of bitopic ligands and developed a structure-based protocol for designing bitopic compounds with desired pharmacological profile.
Book ChapterDOI
Cannabinoid receptor CB1 and CB2 interacting proteins: Techniques, progress and perspectives.
TL;DR: A review of the current state of the literature regarding the cannabinoid receptor interactome is provided in this article, along with a commentary on the methodologies and techniques utilized, and discusses future perspectives.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
Deletion of CB2 Cannabinoid Receptor Induces Schizophrenia-Related Behaviors in Mice
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Journal ArticleDOI
Brain Cannabinoid CB2 Receptor in Schizophrenia
Hiroki Ishiguro,Yasue Horiuchi,Maya Ishikawa,Minori Koga,Keiko Imai,Yoshimi Suzuki,Miyuki Morikawa,Toshiya Inada,Yuichiro Watanabe,Makoto Takahashi,Toshiyuki Someya,Hiroshi Ujike,Nakao Iwata,Norio Ozaki,Emmanuel S. Onaivi,Hiroshi Kunugi,Tsukasa Sasaki,Masanari Itokawa,Makoto Arai,Kazuhiro Niizato,Shyuji Iritani,Izumi Naka,Jun Ohashi,Akiyoshi Kakita,Hitoshi Takahashi,Hiroyuki Nawa,Tadao Arinami +26 more
TL;DR: Findings indicate an increased risk of schizophrenia for people with low CB2 receptor function, as well as nominally significant associations between schizophrenia and two SNPs.
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