Figure 2

Effects of TRPM8 antagonists on body temperature (T _b ) in rats or mice. Data are presented as mean ± S.E.M. of temperature collected for every 10 min. Statistical significance is relative to the vehicle (one tail unpaired t-test). Baseline T_b was collected for 20–30 min before compound administration (p.o.) at time 0 and post dosing every 10 min for 120 min (A) or 240 min ( B &C). The stress-induced transient increase in T_b seen right after antagonist administration is indicated by vertical dotted lines. A) AMG8788 dosed at 30 mg/kg significantly decreased rat T_b by 0.53°C at 40 min (t ₁₀ = 2.55; p < 0.05). B) AMG2850 dosed at 100 mg/kg significantly decreased rat T_b by 0.98°C at 140 min (t ₁₀ = 4.38; p < 0.001). C) AMG2850 dosed at 100 mg/kg significantly decreased mouse T_b by 0.73°C at 100 min (t ₁₇ = 2.99; p < 0.001). D) TRPM8 antagonist AMG9678 induced decrease in body temperature is transient in nature. Statistical significance is relative to vehicle (one way ANOVA followed by Dunnett’s Multiple Comparison Test). Baseline T_b was collected at 30 min before compound administration (p.o.) at time 0 and post dosing every 1 h for 24 h. At 100 mg/kg, AMG9678 significantly decreased T_b by 0.83°C at 1 hour (F _3,22 = 6.46, p < 0.01), whereas at the same time, the maximum decrease of T_b was 0.7 and 0.72 ⁰ C at 30 mg/kg and 10 mg/kg, respectively.