The effect of prototypic sigma ligands on the binding of [3H]dextromethorphan to guinea pig brain.
The effect of prototypic sigma ligands on the binding of [3H]dextromethorphan to guinea pig brain.
复制标题
原型西格玛配体对[3H]右美沙芬与豚鼠脑结合的影响。
DOI：
10.1016/0304-3940(89)90159-6
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发表时间：
1989
影响因子：
2.5
通讯作者：
Musacchio,JM
中科院分区：
文献类型：
--
作者：
Klein,M;Paturzo,JJ;Musacchio,JM
我们研究了几种典型的σ位点配体对[~3H]右美沙芬([~3H]DM)与豚鼠脑结合的影响。氟哌啶醇、3-(-3-羟基苯基)-N-(1-丙基)哌啶((+)-3-PPP)和(+)-N-烯丙基-N-去甲氧基偶氮唑((+)-NANM或(+)-SKF10,047)是有效的σ位点配体，对[~3H]DM结合位点表现出较高的亲和力。如高亲和力位点的Ki值所示，σ配体的效力等级顺序为：氟哌啶醇；(+)-五唑酮；(+)-环唑嘌呤；(+)-SKF10,047；(−)-丁酰胺醇；(+)-丁酰胺醇；(−)-SKF10,047。这个效价顺序类似于标记有[~3H](+)-3-PPP和[~3H](+)-SKF10,047的位点。几种苯并吗啉的(+)-异构体表现出比(−)-异构体更高的亲和力，(−)-丁二醇比(+)-异构体更有效地与[~3H]DM竞争，表现出与σ位点相同的立体专一性。这里报告的发现表明，DM和σ网站之间存在以前未被认识到的相似之处。显然，有必要进一步探索DM、σ和苯环利定(PCP)部位，以确定这些部位的生理作用和治疗潜力。
We studied the effects of several prototypic σ site ligands on the binding of [3H]dextromethorphan ([3H]DM) to guinea pig brain. Haloperidol, 3-(-3-Hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) and (+)-N-allyl-N-normetazocine ((+)-NANM or (+)-SKF10,047), which are potent σ site ligands, showed high affinity for [3H]DM binding sites. The rank order of potency of σ ligands, as indicated by theKivalues for the high-affinity sites is: haloperidol >(+)-pentazocine >(+)-cyclazocine >(+)-SKF10,047 >(−)-butaclamol > (+)-butaclamol >(−)-SKF10,047. This rank order of potency is similar to that for the sites labeled with [3H](+)-3-PPP and [3H](+)-SKF10,047. The (+)-isomers of several benzomorphans displayed higher affinity than the (−)-isomers, (−)-Butaclamol competed against [3H]DM binding more effectively than the (+)-isomer, displaying the same stereospecificity shown for σ sites. The findings reported here demonstrate that there are previously unrecognized similarities between DM and σ sites. It is evident that further exploration of the DM, σ and phencyclidine (PCP) sites will be necessary to establish the physiological role and therapeutic potential of these sites.