Löscher W
Arch Int Pharmacodyn Ther. 1985 Aug;276(2):263-70.
The anticonvulsant efficacy of the GABAmimetic drugs cetyl GABA, progabide and THIP (4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-ol) was studied against minor (myoclonic) and major (generalized tonic-clonic) seizures in gerbils as well as against maximal electroshock and s.c. pentylenetetrazol-induced seizures in mice. Seizures in gerbils were evoked by a blast of compressed air. THIP and progabide were about equally active to protect gerbils against minor and major seizures. ED 50s for THIP were 0.98 and 1.3 mg/kg and for progabide 58 and 50 mg/kg i.p., respectively. Cetyl GABA failed to show a linear dose-response against minor seizures but was quite potent against major ones (ED 50 4.4 mg/kg). All three GABAmimetics were inactive in the mouse models of seizure states except a weak effect of progabide against maximal electroshock seizures. The data show that seizure-prone gerbils with different seizure types differ strikingly in sensitivity to GABAmimetic drugs from traditional mouse models for anticonvulsant drug evaluation.
研究了拟γ-氨基丁酸（GABA）药物十六烷基GABA、普罗加比和THIP（4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇）对沙土鼠轻微（肌阵挛性）和严重（全身性强直阵挛性）癫痫发作的抗惊厥效力，以及对小鼠最大电休克和皮下注射戊四氮诱发癫痫发作的抗惊厥效力。沙土鼠的癫痫发作由一阵压缩空气诱发。THIP和普罗加比在保护沙土鼠免受轻微和严重癫痫发作方面的活性大致相同。THIP的半数有效剂量（ED50）分别为腹腔注射0.98和1.3mg/kg，普罗加比为58和50mg/kg。十六烷基GABA对轻微癫痫发作未呈现线性剂量反应，但对严重癫痫发作相当有效（ED50为4.4mg/kg）。除普罗加比对最大电休克癫痫发作有微弱作用外，所有三种拟GABA药物在癫痫发作状态的小鼠模型中均无活性。数据表明，具有不同癫痫发作类型的癫痫易感沙土鼠与用于抗惊厥药物评估的传统小鼠模型相比，对拟GABA药物的敏感性存在显著差异。
