Klein M, Paturzo J J, Musacchio J M
Department of Pharmacology, N.Y.U. Medical Center, New York 10016.
Neurosci Lett. 1989 Feb 13;97(1-2):175-80. doi: 10.1016/0304-3940(89)90159-6.
We studied the effects of several prototypic sigma 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 sigma site ligands, showed high affinity for [3H]DM binding sites. The rank order of potency of sigma ligands, as indicated by the Ki values for the high-affinity sites is: haloperidol greater than (+)-pentazocine greater than (+)-cyclazocine greater than (+)-SKF10,047 greater than (-)-butaclamol much greater than (+)-butaclamol greater than (-)-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 sigma sites. The findings reported here demonstrate that there are previously unrecognized similarities between DM and sigma sites. It is evident that further exploration of the DM, sigma and phencyclidine (PCP) sites will be necessary to establish the physiological role and therapeutic potential of these sites.
我们研究了几种原型西格玛位点配体对[3H]右美沙芬（[3H]DM）与豚鼠脑结合的影响。强效西格玛位点配体氟哌啶醇、3 - (-3 - 羟基苯基)-N-(1 - 丙基)哌啶[ (+)-3 - PPP]和(+)-N - 烯丙基 - N - 去甲左啡诺[ (+)-NANM或(+)-SKF10,047]对[3H]DM结合位点显示出高亲和力。高亲和力位点的Ki值所表明的西格玛配体效力的等级顺序为：氟哌啶醇大于(+)-喷他佐辛大于(+)-环唑辛大于(+)-SKF10,047大于(-)-布他拉莫远大于(+)-布他拉莫大于(-)-SKF10,047。这种效力等级顺序与用3H-3 - PPP和3H-SKF10,047标记的位点相似。几种苯并吗啡烷的(+)-异构体比(-)-异构体表现出更高的亲和力。(-)-布他拉莫比(+)-异构体更有效地竞争[3H]DM结合，显示出与西格玛位点相同的立体特异性。此处报道的研究结果表明，DM和西格玛位点之间存在以前未被认识到的相似性。显然，有必要进一步探索DM、西格玛和苯环己哌啶（PCP）位点，以确定这些位点的生理作用和治疗潜力。
