Modulation of CB1 cannabinoid receptor by allosteric ligands: Pharmacology and therapeutic opportunities. (15th September 2017)

• Record Type: Journal Article
• Authors: Khurana, Leepakshi; Mackie, Ken; Piomelli, Daniele; Kendall, Debra A.
• Is Part Of: Neuropharmacology. Volume 124(2017)
• Page Start: 3
• Page End: 12
• Publication Date: 2017-09-15
• Subjects: CB1 -- Allosteric modulator -- Biased signaling -- Therapeutic potential; CB1 cannabinoid receptor one -- GPCR G-protein coupled receptors -- PAM positive allosteric modulators -- NAM negative allosteric modulators -- SAM silent allosteric modulators -- PTX pertussis-toxin -- 2-AG 2-arachidonylglycerol -- LXA4 lipoxin A4 -- LOX 5-lipoxygenase -- TM transmembrane helices -- CNS central nervous system -- THC Δ9-tetrahydrocannabinol; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2017.05.018
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Cannabinoid pharmacology has been intensely studied because of cannabis' pervasive medicinal and non-medicinal uses as well as for the therapeutic potential of cannabinoid-based drugs for the treatment of pain, anxiety, substance abuse, obesity, cancer and neurodegenerative disorders. The identification of allosteric modulators of the cannabinoid receptor 1 (CB1 ) has given a new direction to the development of cannabinoid-based therapeutics due to the many advantages offered by targeting allosteric site(s). Allosteric receptor modulators hold potential to develop subtype-specific and pathway-specific therapeutics. Here we briefly discuss the first-generation of allosteric modulators of CB1 receptor, their structure-activity relationships, signaling pathways and the allosteric binding site(s) on the CB1 receptor. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology". Highlights: Modulation of the CB1 receptor by allosteric modulators is an area of intense research. Receptor subtype and pathway specificity can be achieved by allosteric modulators of the CB1 receptor. Different allosteric modulators and their impact on signaling pathways is revealed though complexities are apparent. Putative allosteric binding site(s) on the CB1 receptor are examined.