Bowery N G, Hill D R, Hudson A L
Neuropharmacology. 1982 May;21(5):391-5. doi: 10.1016/0028-3908(82)90021-1.
The compound SL75102 ([alpha(4-chlorophenyl)5-fluoro 2-hydroxy benzilidene-amino]-4-butanoate sodium) is a GABA-mimetic at bicuculline-sensitive and -insensitive receptors. It depolarized rat isolated superior cervical ganglia in a dose-dependent manner (relative potency = 0.101 +/- 0.013; GABA = 1). Bicuculline methobromide (13 microM) antagonized this action of SL75102 and shifted the log dose-response curve to the same extent as the GABA curve. The evoked release of [3H]noradrenaline from rat isolated atria was also reduced by SL75102 in a GABA-like manner. SL75102 also displaced [3H]GABA and [3H]baclofen specifically bound to divalent cation dependent GABAB sites on rat synaptic membranes (relative potency approximately 0.1 GABA throughout). The butyramide from which SL75102 can be formed within the body (SL76002) was much less active at GABAB sites (less than 0.02 atria, 0.001 binding, GABA = 1). It is suggested that in addition to any direct action of SL76002 itself the products of SL76002 metabolism, SL75102 and GABA may exert effects via baclofen-sensitive GABAB as well as GABAA sites in mammalian brain.
化合物SL75102（[α-（4-氯苯基）-5-氟-2-羟基亚苄基氨基]-4-丁酸酯钠）在对荷包牡丹碱敏感和不敏感的受体上是一种γ-氨基丁酸（GABA）模拟物。它以剂量依赖的方式使大鼠离体颈上神经节去极化（相对效价 = 0.101 ± 0.013；GABA = 1）。甲基溴化荷包牡丹碱（13 μM）拮抗了SL75102的这一作用，并使对数剂量反应曲线的位移程度与GABA曲线相同。SL75102还以类似GABA的方式减少了从大鼠离体心房诱发释放的[³H]去甲肾上腺素。SL75102还特异性地取代了与大鼠突触膜上二价阳离子依赖性GABAB位点结合的[³H]GABA和[³H]巴氯芬（整个过程中相对效价约为0.1 GABA）。在体内可由其形成SL75102的丁酰胺（SL76002）在GABAB位点的活性要低得多（心房活性小于0.02，结合活性为0.001，GABA = 1）。有人提出，除了SL76002本身的任何直接作用外，SL76002代谢产物SL75102和GABA可能通过对巴氯芬敏感的GABAB以及哺乳动物脑中的GABAA位点发挥作用。
