Fig 1.
Z944 has no anti-seizure effect in fully kindled animals.
(A) Z944 does not suppress seizures in fully kindled animals compared to vehicle treatment. Carbamazepine (CBZ, n = 7) significantly reduced the class of seizure elicited when compared to vehicle (p<0.05). (B) All four doses of Z944, ETX and CBZ did not affect the primary after discharge when compared to vehicle (p>0.5). (C) Total seizure duration was unaffected in all treatment groups. (D) Adverse effects of Z944 are dose dependent. Z944 (100 mg/kg) and CBZ showed significantly higher adverse effects when compared to vehicle, (p<0.01 for both treatments). *p<0.05, **p<0.01. Kruskal-Wallis test with Dunns post-hoc test.
Fig 2.
Z944 delays the progression to kindling.
(A) Animals receiving Z944 (n = 7, 30 mg/kg) required significantly more stimulations to evoke a class III (p<0.05), IV (p<0.01) or V (p<0.0001) seizure than the animals receiving vehicle (n = 6) and required more stimulations to reach class V (p<0.01) when compared to ethosuximide (ETX, n = 6, 100 mg/kg) treated animals. (B) Z944 treated animals (n = 7, 30 mg/kg) required significantly more stimulations to reach the fully kindled state when compared to vehicle (n = 6, p<0.01) and ETX (n = 6, 100 mg/kg, p<0.05) treatment groups. (C) There was no significant difference in average seizure duration between the three treatment groups. *p<0.05, **p<0.01, ****p<0.0001 Z944 vs vehicle. #p<0.05, ##p<0.01 Z944 vs ETX. (A) and (C) Two way repeated measures ANOVA with Bonferroni post-hoc test. (B) One way ANOVA with Bonferroni post-hoc test.