Time-course response in the rat CCI cold allodynia model following oral dosing of 10 mg/kg of 5 (red down-pointing triangle), 64 (green diamond), 65 (red up-pointing triangle), and 66 (violet circle) vs vehicle (20% HPβCD po; gray square)

June 07, 2024

• Title:       

  Time-course response in the rat CCI cold allodynia model following oral dosing of 10 mg/kg of 5 (red down-pointing triangle), 64 (green diamond), 65 (red up-pointing triangle), and 66  (violet circle) vs vehicle (20% HPβCD po; gray square)

• Image Source:

  Design and optimization of benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonists

• Mark:

  Figure 2

• Associated context:

  The potent TRPM8 antagonists 5 and 64-66, which displayed relatively high metabolic stability and the lowest CYP 2C9 inhibitory activities, were further scrutinized in the WDS  PD assay. All four compounds completely prevented icilininduced WDS at oral doses of 10 mg/kg; therefore, the rat  CCI cold allodynia model was used as a means to discriminate the compounds. All compounds demonstrated efficacy in the  CCI model, albeit to different degrees. At an oral dose of  10 mg/kg, 5 gave the greatest reversal of 91%, whereas 64-66  peaked at 51%, 74%, and 74%, respectively, after 2 h postdose  (Figure 2).