Decahydroquinoline amides as highly selective CB2 agonists: Role of selectivity on in vivo efficacy in a rodent model of analgesia
2011
Manley, Peter J. | Zartman, Amy | Paone, Daniel V. | Burgey, Christopher S. | Henze, Darrell A. | Penna, Kimberly Della | Desai, Reshma | Leitl, Michael D. | Lemaire, Wei | White, Rebecca B. | Yeh, Suzie | Urban, Mark O. | Kane, Stefanie A. | Hartman, George D. | Bilodeau, Mark T. | Trotter, B Wesley
A novel series of decahydroquinoline CB2 agonists is described. Optimization of the amide substituent led to improvements in CB2/CB1 selectivity as well as physical properties. Two key compounds were examined in the rat CFA model of acute inflammatory pain. A moderately selective CB2 agonist was active in this model. A CB2 agonist lacking functional CB1 activity was inactive in this model despite high in vivo exposure both peripherally and centrally.
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