Table 7

Comparison of acute oral efficacy (MES, mg/kg) and safety (TD₅₀-inverted screen for mice and plank walk for rats) of [S]-AR-R 15896AR, [R]-AR-R 15895AR, and [R,S]-AR-R 15035AR to known antiepileptic drugs

Compound	Mice		Rats
Compound	MES ED₅₀	TD₅₀	TI	MES ED₅₀	TD₅₀	TI
[S]-AR-R 15896AR	17.3 [15–19]	193 [145–235]	11.2	3.7 [3–6]	933 [712–2361]	252
[R]-AR-R 15895AR	57.3 [49–69]	142 [80–226]	2.5	20.2 [10–35]	>1000	>49.5
[R,S]-AR-R 15035AR	17.5 [14–21]	245 [139–359]	14.0	10 [4–17]	>1000	>100
Carbamazepine^7-150 ^, ^7-160	13.0 [12–16]	137 [122–153]	10.2	4.0 [3–6]	571 [421–775]	143
Phenytoin^7-160	16.8 [15–19]	234 [131–354]	13.9	13.3 [11–16]	>2000	>150
Valproate^7-150 ^, ^7-160	631 [522–757]	>2000	>3	261 [216–301]	578 [482–752]	2.2
Phenobarbital^7-160	21.2 [19–25]	108 [93–125]	5.1	3.4 [2–5]	71 [63–80]	20.9
Lamotrigine	6.1 [5–7]	71.6 [49–98]	11.7	1.2 [1–2]	>60	>50
Felbamate	45.6 [43–53]	>1000	>22	26.7 [20–34]	>600	>22.5
Flunarizine	35.6 [30–42]	>500	>14	6.9 [5–10]	ND	ND

↵7-150 Mouse data from Stagnitto et al. (1990).
↵7-160 Rat data from Garske et al. (1991). Prior to testing for anticonvulsant efficacy or safety, mice and rats were pretreated with test compounds at 30 and 60 min, respectively (except flunarizine in rats the time of test was 5 h). ED₅₀ and TD₅₀values are in mg/kg, values in brackets are 95% confidence limits.