Neuroleptic receptors: stereoselectivity for neuroleptic enantiomers.
Neuroleptic receptors: stereoselectivity for neuroleptic enantiomers.
复制标题
抗精神病药受体：抗精神病药对映体的立体选择性。
DOI：
10.1016/0014-2999(79)90177-8
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发表时间：
1979
影响因子：
5
通讯作者：
A. Philipp
中科院分区：
文献类型：
--
作者：
P. Seeman;K. Westman;M. Protiva;J. Jílek;P. C. Jain;A. Saxena;N. Anand;L. Humber;A. Philipp
为了鉴定一对与神经安定药/多巴胺受体具有最高立体选择性相互作用的神经安定药对映体，测定了8对神经安定药对映体对~ 3 H-螺哌隆与小牛尾状核粗匀浆特异性结合的影响。Ki值的比值为：（+）-butaclamol/（−）-butaclamol = 3000; dexclamol/（−）-analogue = 151;（+）-isobutaclamol/（−）-isobutaclamol = 146;（−）-CTC/（+）-CTC = 109;（−）-centbutindole/（+）-centbutindole = 20; S（+）-aclothepin/R（−）-aclothepin = 11。因此，精神抑制剂受体对于刚性的布他拉莫衍生物是高度立体选择性的，但对于柔性的精神抑制剂则少得多。然而，3 H-阿扑吗啡结合位点对异丁氨醇的立体选择性比率仅为7，进一步表明3 H-神经安定剂结合和3 H-阿扑吗啡结合的高亲和力位点（即nM）是不同的。
In order to identify a pair of neuroleptic enantiomers with the highest stereoselective interaction with neuroleptic/dopamine receptors, the effects of eight pairs of neuroleptic enantiomers were tested on the specific binding of3H-spiperone to crude homogenates of calf caudate nucleus. The ratios of the Kivalues were: (+)-butaclamol/(−)-butaclamol = 3000; dexclamol/(−)-analogue = 151; (+)-isobutaclamol/(−)-isobutaclamol = 146; (−)-CTC/(+)-CTC = 109; (−)-centbutindole/(+)-centbutindole = 20; S(+)-octoclothepin/R(−)-octoclothepin = 11. Thus, the neuroleptic receptor is highly stereoselective for the rigid butaclamol derivatives, but much less so for the flexible neuroleptics. The3H-apomorphine binding site, however, had a stereoselectivity ratio of only 7 for isobutaclamol, further suggesting that the high affinity sites (i.e. nM) for3H-neuroleptic binding and for3H-apomorphine binding are different.