(4S)-4-Amino-5,6-heptadienoic acid [S)-gamma-allenyl-GABA; MDL 72483) is a potent inactivator of brain GABA-T in mice; (ED50 (i.p.) = 60 mg.kg-1; ED50 (oral) = 70 mg.kg-1). Its anticonvulsant effects against 3-mercaptopropionic acid (MPA)-induced seizures in mice is related to the elevation of whole brain GABA concentrations: The mentioned doses of MDL 72483 which cause a decrease of GABA-T activity by 50%, produce within 5 h after dosing an increase of GABA concentration by about 3 mumol.g-1, and protect 50% of the mice against seizures in this model of presynaptic GABA deficit. When given orally MDL 72483 is about five times more potent than vigabatrin [4R/S)-4-amino-5-hexenoic acid) a known antiepileptic GABA-T inhibitor. Complete protection was achieved with a dose of 150 mg.kg-1. Similar to vigabatrin, MDL 72483 does not protect significantly against metrazol-induced convulsions. However, at a dose of 300 mg.kg-1, the time elapsing between metrazol administration and onset of convulsions was prolonged by a factor of 3.4. Oral administration of MDL 72483 for up to 19 days at a daily dose of 91-96 mg.kg-1 did not produce any obvious behavioral changes in mice, nor was the ED50 of the drug in MPA-seizure tests significantly altered by the pretreatment. These observations indicate that MDL 72483 is a promising drug for the treatment of certain epilepsies.

中文翻译：

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（4S）-4-氨基-5,6-庚二烯酸（MDL 72483）：一种有效的抗惊厥性GABA-T抑制剂。

（4S）-4-氨基-5,6-庚二烯酸[S）-γ-烯基-GABA；MDL 72483）是小鼠脑GABA-T的有效灭活剂；（ED50（ip）= 60 mg.kg-1； ED50（口服）= 70 mg.kg-1）。它对3-巯基丙酸（MPA）诱发的癫痫发作的抗惊厥作用与全脑GABA浓度的升高有关：提及的MDL 72483剂量可导致GABA-T活性降低50％，在5小时内产生在这种突触前GABA缺乏模型中，给药后GABA浓度增加了约3μmol.g-1，并保护了50％的小鼠免于癫痫发作。口服MDL 72483的效价比已知抗癫痫性GABA-T抑制剂vigabatrin [4R / S）-4-氨基-5-己烯酸的效力高约五倍。150 mg.kg-1的剂量可实现完全保护。与vigabatrin相似，MDL 72483不能明显预防甲硝唑引起的惊厥。但是，以300 mg.kg-1的剂量服用甲硝唑与抽搐发作之间的时间延长了3.4倍。每天以91-96 mg.kg-1的剂量口服MDL 72483长达19天，在小鼠中未产生任何明显的行为变化，并且在MPA癫痫发作试验中该药物的ED50也未因预处理而显着改变。这些观察结果表明，MDL 72483是用于治疗某些癫痫的有前途的药物。kg-1不会在小鼠中产生任何明显的行为变化，MPA癫痫发作试验中药物的ED50也不因预处理而显着改变。这些观察结果表明，MDL 72483是用于治疗某些癫痫的有前途的药物。kg-1不会在小鼠中产生任何明显的行为变化，MPA癫痫发作试验中药物的ED50也不因预处理而显着改变。这些观察结果表明，MDL 72483是用于治疗某些癫痫的有前途的药物。