Fig. 4.
Increased number of MC before GTC occurs with TGB but not CLN or combined treatment because of increased duration and peak rate of MC before GTC. (A) TGB dose-dependently increases number of MC before GTC. The mean number of MC before GTC (± S.E.M.) is shown. (B) TGB increases duration and peak rate of MC. Mean MC rate leading up to GTC (time 0) for equally effective doses of CLN, TGB, and 1:1 ratio (red CLN 2.5 mg/kg; blue TGB 10 mg/kg; green 1:1 ratio, 0.6 mg/kg; control black). MC seizures began earliest (−700 seconds) and reached the highest rate (0.9 MC/s) with TGB treatment. Onset relative to GTC and maximal rate of MC was not different among control (−300 seconds, 0.1 MC/s), CLN (−300 seconds, 0.19 MC/s), and 1:1 ratio (−300 seconds, 0.15 MC/s). (C) Increased duration of MC activity with TGB treatment is associated with a greater difference in temperature between MC and GTC. Number of MC seizures in each 0.1°C temperature bin before GTC at the maximally effective dose of TGB (10 mg/kg) and doses of CLN (2.5 mg/kg) and 1:1 ratio (0.6 mg/kg) providing equal protection against GTC. MC begins at slightly higher temperatures than does control with TGB (inset), and the number of MC increases substantially with temperature. MC does not increase until high temperatures with CLN or 1:1 ratio. Mean temperatures (± S.E.M.) at MC and GTC are as follows: control, 38.1 ± 0.2°C and 38.5 ± 0.2°C; CLN, 41.0 ± 0.2°C and 41.4 ± 0.1°C; 1:1 ratio, 41.0 ± 0.2°C and 41.1 ± 0.3°C; and TGB, 38.9 ± 0.3°C and 41.2 ± 0.2°C. In B and C, CLN, red, n = 8; 1:1 ratio, green, n = 10; TGB, blue, n = 10.