Karbon E W, Naper K, Pontecorvo M J
Nova Pharmaceutical Corporation, Baltimore, MD 21224-2788.
Eur J Pharmacol. 1991 Jan 25;193(1):21-7. doi: 10.1016/0014-2999(91)90195-v.
The interaction of various compounds with sigma binding sites was examined in membranes prepared from whole guinea pig brain. Whereas 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine labeled a single population of binding sites exhibiting a Kd of 43 nM, [3H]1,3-di-o-tolylguanidine bound to two sites having Kds of 35 and 212 nM, and to a greater maximum number of sites than 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. Haloperidol, 1,3-di-o-tolylguanidine, BMY 14802, and (-)-pentazocine each displayed nearly equal affinity for binding sites labeled by 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine and [3H]1,3-di-o-tolylguanidine, whereas (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine was 3 times more potent in inhibiting 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine than [3H]1,3-di-o-tolylguanidine binding. In contrast, (+)-SKF 10,047, (+)-cyclazocine and (+)-pentazocine exhibited more than 9-fold higher affinity for 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine than [3H]1,3-di-o-tolylguanidine binding sites. Dextromethorphan was 15-fold more potent against 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine than [3H]1,3-di-o-tolylguanidine, inhibited 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine binding in a biphasic manner, and inhibited [3H]haloperidol and 3H-SKF 10,047 binding with potencies similar to those obtained against [3H]1,3-di-o-tolylguanidine and 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, respectively. Phenytoin increased 3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine and 3H-SKF 10,047 binding, but did not enhance [3H]1,3-di-o-tolylguanidine or [3H]haloperidol binding. However, the potency of dextromethorphan to inhibit [3H]1,3-di-o-tolylguanidine binding was increased in the presence of phenytoin.(ABSTRACT TRUNCATED AT 250 WORDS)
在从豚鼠全脑制备的膜中检测了各种化合物与σ结合位点的相互作用。3H-3-(3-羟基苯基)-N-(1-丙基)哌啶标记了一群单一的结合位点，其解离常数（Kd）为43 nM，而[3H]1,3-二邻甲苯基胍与两个位点结合，其Kd分别为35和212 nM，且结合位点的最大数量比3H-3-(3-羟基苯基)-N-(1-丙基)哌啶更多。氟哌啶醇、1,3-二邻甲苯基胍、BMY 14802和(-)-喷他佐辛对3H-3-(3-羟基苯基)-N-(1-丙基)哌啶和[3H]1,3-二邻甲苯基胍标记的结合位点表现出几乎相等的亲和力，而(+)-3-(3-羟基苯基)-N-(1-丙基)哌啶在抑制3H-3-(3-羟基苯基)-N-(1-丙基)哌啶结合方面的效力是抑制[3H]1,3-二邻甲苯基胍结合的3倍。相比之下，(+)-SKF 10,047、(+)-环唑辛和(+)-喷他佐辛对3H-3-(3-羟基苯基)-N-(1-丙基)哌啶结合位点的亲和力比对[3H]1,3-二邻甲苯基胍结合位点的亲和力高9倍以上。右美沙芬抑制3H-3-(3-羟基苯基)-N-(1-丙基)哌啶结合的效力比对[3H]1,3-二邻甲苯基胍高15倍，以双相方式抑制3H-3-(3-羟基苯基)-N-(1-丙基)哌啶结合，并且抑制[3H]氟哌啶醇和3H-SKF 10,047结合的效力分别与抑制[3H]1,3-二邻甲苯基胍和3H-3-(3-羟基苯基)-N-(1-丙基)哌啶结合的效力相似。苯妥英增加了3H-3-(3-羟基苯基)-N-(1-丙基)哌啶和3H-SKF 10,047的结合，但没有增强[3H]1,3-二邻甲苯基胍或[3H]氟哌啶醇的结合。然而，在苯妥英存在的情况下，右美沙芬抑制[3H]1,3-二邻甲苯基胍结合的效力增加。（摘要截短于250字）
