Table 2.
Anticonvulsant activity and neurotoxicity of compounds in the MES and scMET models following intraperitoneal (ip.) administration in mice.
| Compound | Dose (mg/kg) | MES a | scMET b | TOX c | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0.5 h | 4.0 h | 0.5 h | 4.0 h | 0.5 h | 4.0 h | ||||||||
| (4R,8aR)-3a | 100 | 0/3 | 0/3 | 0/1 | 0/1 | 0/8 | 0/4 | ||||||
| 300 | 1/1 | 0/1 | 1/1 | 0/1 | 4/4 | 0/2 | |||||||
| (4S,8aS)-3b | 100 | 0/3 | 0/3 | 0/1 | 0/1 | 0/8 | 0/4 | ||||||
| 300 | 1/1 | 0/1 | 0/1 | 0/1 | 0/4 | 0/2 | |||||||
| (4R,8aR)-3b | 100 | 0/3 | 0/3 | 0/1 | 0/1 | 0/8 | 0/4 | ||||||
| 300 | 1/1 | 0/1 | 0/1 | 0/1 | 0/4 | 0/2 | |||||||
| (4S,9aS)-3c | 100 | 1/3 | 0/3 | 0/1 | 0/1 | 0/8 | 0/4 | ||||||
| 300 | 1/1 | 0/1 | 5/5 | 0/1 | 04 | 0/2 | |||||||
| (4R,9aR)-3c | 100 | 1/3 | 0/3 | 0/1 | 0/1 | 0/8 | 0/4 | ||||||
| 300 | 1/1 | 0/1 | 0/1 | 0/1 | 4/4 d,e | 2/2 d | |||||||
| (4S,8aS)-3d | 100 | 0/4 | 0/4 | - f | - | 0/4 | 0/4 | ||||||
| 300 | - | - | - | - | - | - | |||||||
| (4R,8aR)-3d | 100 | 0/4 | 0/4 | - | - | 0/4 | 0/4 | ||||||
| 300 | - | - | - | - | - | - | |||||||
| (8aS)-3e | 100 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | ||||||
| 300 | - | - | - | - | - | - | |||||||
| (8aR)-3e | 100 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | ||||||
| 300 | - | - | - | - | - | - | |||||||
| (8aS)-3f | 100 | 0/1 | 0/1 | 0/1 | 0/1 | 3/8 | 1/4 d | ||||||
| 300 | 0/3 | 0/2 | 0/1 | 0/1 | 4/4 g | 0/4 | |||||||
| (8aS)-3g | 100 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | ||||||
| 300 | - | - | - | - | - | - | |||||||
| (4S,8aS)-3h | 100 | 3/4 h | 0/4 | 0/4 | 0/4 | 0/8 | 0/8 | ||||||
| 300 | - | - | - | - | - | - | |||||||
| (4S,8aS)-6 | 100 | 3/4 | 3/4 | 0/4 | 0/8 | 0/8 | 0/8 | ||||||
| 300 | - | - | - | - | - | - | |||||||
| (4R,8aR)-6 | 100 | 3/4 | 0/4 | 0/4 | 0/8 | 0/8 | 0/8 | ||||||
| 300 | - | - | - | - | - | - | |||||||
a Maximal electroshock test (number of animals protected/number of animals tested); b Subcutaneous Metrazole test (number of animals protected/number of animals tested); c Neurotoxicity test (number of animals exhibiting neurological toxicity/number of animals tested); d One animal died; e Unable to grasp rotorod; f Not determined; g Four animals died; h Active also in 1/4 at 0.25 h post administration.