Taylor C P, Vartanian M G, Andruszkiewicz R, Silverman R B
Department of Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert, Ann Arbor, MI 48105-2430.
Epilepsy Res. 1992 Apr;11(2):103-10. doi: 10.1016/0920-1211(92)90044-t.
Recently we showed that 3-alkyl-4-aminobutanoic acids are in vitro activators of brain L-glutamic acid decarboxylase (GAD) that show anticonvulsant activity. Since activation of GAD leads to increased concentrations of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in vitro, these compounds could represent a new class of anticonvulsant agents. Here it is shown that 3-alkylglutamic acid analogues also activate GAD and that all of the compounds in both series are active anticonvulsant agents against low intensity electroshock in mice. The most active compound, 3-isobutyl GABA, was tested further against maximal electroshock in mice and was shown to be very potent after both intravenous and oral administration without causing ataxia. It is not known if brain GABA levels are elevated in vivo by administration of these compounds or if the mechanism of anticonvulsant activity is related to their ability to activate GAD.
最近我们发现，3-烷基-4-氨基丁酸是脑L-谷氨酸脱羧酶（GAD）的体外激活剂，具有抗惊厥活性。由于在体外激活GAD会导致抑制性神经递质γ-氨基丁酸（GABA）浓度升高，这些化合物可能代表一类新型抗惊厥药物。本文表明，3-烷基谷氨酸类似物也能激活GAD，并且这两个系列中的所有化合物都是针对小鼠低强度电击的活性抗惊厥剂。对活性最强的化合物3-异丁基GABA进一步进行了小鼠最大电击试验，结果表明，静脉注射和口服后它都非常有效，且不会引起共济失调。目前尚不清楚给予这些化合物后体内脑GABA水平是否升高，也不清楚抗惊厥活性机制是否与其激活GAD的能力有关。
