Suzuki T, Kurosawa H, Naito K, Otsuka M, Ohashi M, Takaiti O
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Eur J Pharmacol. 1991 Mar 5;194(2-3):195-200. doi: 10.1016/0014-2999(91)90105-y.
The binding properties of a new 1,5-benzothiazepine, clentiazem (TA-3090), were investigated in rat cerebral cortex and skeletal muscle membranes with [3H]diltiazem and [3H]nitrendipine as radioligands. Clentiazem inhibited [3H]diltiazem binding to cerebral cortex membranes at the same concentrations as diltiazem at 2 degrees C. However, at 37 degrees C clentiazem was 3 times more potent to inhibit binding than diltiazem. [3H]Nitrendipine binding was modulated by clentiazem in a temperature-dependent manner. At 37 degrees C clentiazem significantly enhanced [3H]nitrendipine binding to rat cerebral cortex membranes, whereas it has an inhibitory effect on [3H]nitrendipine binding at 0 degree C and no effect at 25 degrees C. Of two optical isomers of clentiazem and four of diltiazem, only d-cis isomers (clentiazem and diltiazem) increased [3H]nitrendipine binding, indicating that both compounds have the same stereoselectivity for increasing [3H]nitrendipine binding. These results suggest that clentiazem binds to the same 1,5-benzothiazepine binding sites as diltiazem but with greater affinity.
以[³H]地尔硫䓬和[³H]尼群地平作为放射性配体，在大鼠大脑皮层和骨骼肌膜中研究了一种新型1,5-苯并硫氮䓬——克仑硫䓬（TA-3090）的结合特性。在2℃时，克仑硫䓬抑制[³H]地尔硫䓬与大脑皮层膜结合的浓度与地尔硫䓬相同。然而，在37℃时，克仑硫䓬抑制结合的效力是地尔硫䓬的3倍。克仑硫䓬以温度依赖的方式调节[³H]尼群地平的结合。在37℃时，克仑硫䓬显著增强[³H]尼群地平与大鼠大脑皮层膜的结合，而在0℃时对[³H]尼群地平的结合有抑制作用，在25℃时无影响。在克仑硫䓬的两种光学异构体和地尔硫䓬的四种光学异构体中，只有d-顺式异构体（克仑硫䓬和地尔硫䓬）增加了[³H]尼群地平的结合，这表明这两种化合物在增加[³H]尼群地平结合方面具有相同的立体选择性。这些结果表明，克仑硫䓬与地尔硫䓬结合于相同的1,5-苯并硫氮䓬结合位点，但亲和力更高。
