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Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor

Acta Pharmacologica Sinicavolume 40pages324335 (2019) | Download Citation



The cannabinoid type-1 (CB1) receptor, a G-protein-coupled receptor, is an attractive target for drug discovery due to its involvement in many physiological processes. Historically, drug discovery efforts targeting the CB1 receptor have focused on the development of orthosteric ligands that interact with the active site to which endogenous cannabinoids bind. Research performed over the last several decades has revealed substantial difficulties in translating CB1 orthosteric ligands into druggable candidates. The difficulty is mainly due to the adverse effects associated with orthosteric CB1 ligands. Recent discoveries of allosteric CB1 modulators provide tremendous opportunities to develop CB1 ligands with novel mechanisms of action; these ligands may potentially improve the pharmacological effects and enhance drug safety in treating the disorders by regulating the functions of the CB1 receptor. In this paper, we review and summarize the complex pharmacological profiles of each class of CB1 allosteric modulators, the development of new classes of CB1 allosteric modulators and the results from in vivo assessments of their therapeutic value.

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This work was partially supported by NIH Grant DA039942. The authors thank Mrs. Michelle Walbeck for assisting with the revision of this manuscript.

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  1. Rangel College of Pharmacy, Texas A&M University, Kingsville, TX, 78363, USA

    • Dai Lu
    • , Sri Sujana Immadi
    •  & Zhixing Wu
  2. Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA

    • Debra A. Kendall


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Correspondence to Dai Lu.

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