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Kwang H. Ahn, Mariam M. Mahmoud, Sushma Samala, Dai Lu and Debra A. Kendall Profiling two indole-2-carboxamides for allosteric modulation of the CB1 receptor Journal of Neurochemistry 124

Article first published online: 7 JAN 2013 | DOI: 10.1111/jnc.12115

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The cannabinoid receptor 1 plays a pivotal role in appetite stimulation, anxiety, and motor control. We report the synthesis and characterization of two indole-2-carboxamides as CB1 allosteric modulators: ICAM-a and ICAM-b. Although both compounds enhanced agonist binding, ICAM-b displayed the strongest positive cooperativity and induced G-protein-independent β-arrestin-mediated ERK signaling. This demonstrates that fine tuning CB1functions are achievable by small-molecule-allosteric modulators.

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