Biological Activity
mavatrep is a potent and orally bioavailable antagonist of trpv1 with ic50 value of 4.6 nm [1][2].transient receptor potential vanilloid-1 (trpv1) is a thermosensitive and nonselective cation channel, and is a member of the trp channel superfamily. the channel is activated by acidic ph (<6.8), thermal stimuli (>43℃), and endogenous lipidic mediators (anandamide and oxidative metabolites of linoleic acid) [1].mavatrep is a potent and orally bioavailable trpv1 antagonist. in hek293 cells that stably express human or rat trpv1 (rtrpv1) channels, mavatrep (1 μm) inhibited capsaicin-induced ca2+ influx with ic50 values of 4.6 nm and 21 nm. in whole-cell patch clamp electrophysiology assay, mavatrep concentration-dependently inhibited the activation of htrpv1 channels by ph (5.0) and capsaicin (1 μm) with ic50 values of 6.8 and 23 nm, respectively. mavatrep (0.1 μm) also inhibited 74 ± 8.1% heat-evoked currents mediated by htrpv1 [1].in the cfa model of inflammatory of pain, mavatrep (10 mg/kg po) significantly reversed cfa-induced thermal hypersensitivity with ed50 and ed80 values of 1.8 and 7.8 mg/kg, respectively [1].
References
[1]. parsons wh, calvo rr, cheung w, et al. benzo[d]imidazole transient receptor potential vanilloid 1 antagonists for the treatment of pain: discovery of trans-2-(2-{2-[2-(4-trifluoromethyl-phenyl)-vinyl]-1h-benzimidazol-5-yl}-phenyl)-propan-2-ol (mavatrep). j med chem, 2015, 58(9): 3859-3874.
