Testing of representative aminotriazine compound A in the formalin model of pain.

<p><b>A</b>, Timecourse of flinching binned every minute for each of five cohorts: vehicle, positive control morphine (2 mg/kg), and 10 mg/kg, 30 mg/kg, and 60 mg/kg compound A. All cohorts were n = 8 animals, except morphine was n = 5. <b>B</b>, Total flinches in phase 2 (10 minutes to 40 minutes) (bars and left y-axis) and terminal plasma concentrations of compound A (symbols and right y-axis). Total reduction in phase 2 flinching as percent of vehicle: morphine 68%, 10 mg/kg compound A 32%, 30 mg/kg compound A 66%, 60 mg/kg compound A 85%. Terminal plasma and brain concentrations of compound A: for the 10 mg/kg dose plasma 3.02 uM ± 0.21 μM and brain 0.28 μM ± 0.029 μM; for the 30 mg/kg dose plasma 8.07 μM ± 0.65 μM and brain 0.88 μM ± 0.14 μM; for the 60 mg/kg dose plasma 13.5 μM ± 1.60 μM and brain 1.54 μM ± 0.10 μM (for each dose cohort mean ± SEM, plasma n = 8, brain n = 4). <b>C</b>, Effects of compound A on spontaneous locomotor behaviors. Graph shows basic movement counts (bars and left y-axis) and terminal plasma concentrations (symbols and right y-axis) following indicated doses of compound A. Total percent reduction and the corresponding terminal plasma concentrations: for the 10 mg/kg dose -4.2% and 2.75 μM ± 0.26 μM; for the 30 mg/kg dose 14% and 5.53 μM ± 0.57 μM; for the 60 mg/kg dose 46% and 13.0 μM ± 1.7 μM (brains were not analyzed) (for each dose cohort mean ± SEM, n = 8). **p < 0.01, ***p < 0.001.