Steinfels G F, Tam S W, Cook L
Life Sci. 1986 Dec 29;39(26):2611-5. doi: 10.1016/0024-3205(86)90116-5.
In rats trained to discriminate the prototypic sigma receptor agonist, (+)-N-Allylnormetazocine [(+)-N-Allylnormetazocine [(+)-NANM/SKF 10,047], from saline, the (+)- but not the (-)-isomer of 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) produced (+)-NANM-like discriminative stimuli. (+)-3-PPP binds stereo selectively to the (+)-NANM binding site, but not to the phencyclidine binding site. Additionally, phencyclidine was found to produce (+)-NANM-like discriminative stimuli. Although the 3-PPP isomers were shown to produce changes in central dopaminergic activity (Hjorth et al. Life Sci 37, 673, 1985), the discriminative stimulus properties of (+)-3-PPP are apparently not mediated via the dopaminergic system. This hypothesis is supported by the fact that apomorphine did not produce (+)-NANM-like discriminative stimuli. These stimuli are thus non-dopaminergic and may be due to the (+)-3-PPP actions at the sigma binding site. However, it is possible that (+)-NANM, PCP, and (+)-3-PPP may have common non-sigma pharmacologic properties that account for the similar discriminative stimulus properties of these compounds.
在经过训练以区分原型西格玛受体激动剂（+）-N-烯丙基去甲左啡诺[（+）-N-烯丙基去甲左啡诺[（+）-NANM/SKF 10,047]与生理盐水的大鼠中，3-（3-羟基苯基）-N-（1-丙基）哌啶（3-PPP）的（+）-异构体而非（-）-异构体产生了（+）-NANM样的辨别性刺激。（+）-3-PPP立体选择性地结合到（+）-NANM结合位点，但不结合到苯环己哌啶结合位点。此外，发现苯环己哌啶会产生（+）-NANM样的辨别性刺激。尽管已证明3-PPP异构体可引起中枢多巴胺能活性的变化（Hjorth等人，《生命科学》37, 673, 1985），但（+）-3-PPP的辨别性刺激特性显然不是通过多巴胺能系统介导的。阿扑吗啡不会产生（+）-NANM样的辨别性刺激这一事实支持了这一假设。因此，这些刺激是非多巴胺能的，可能是由于（+）-3-PPP在西格玛结合位点的作用。然而，（+）-NANM、PCP和（+）-3-PPP可能具有共同的非西格玛药理学特性，这可以解释这些化合物相似的辨别性刺激特性。
