Hjorth S, Carlsson A, Clark D, Svensson K, Wikström H, Sanchez D, Lindberg P, Hacksell U, Arvidsson L E, Johansson A, Nilsson J L
J Neural Transm Suppl. 1983;18:131-7.
In the course of a search for new selective dopamine (DA) autoreceptor agonists the DA analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, was resolved into its dextro-(+) and levo-(-) rotatory enantiomers. The compounds were pharmacologically evaluated by means of behavioural and biochemical methods. Surprisingly, both (+)-and (-)-3-PPP show clearcut, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA receptor agonist with activity on autoreceptors as well as postsynaptic receptors, whereas (-)-3-PPP similarly activates DA autoreceptors but, in contrast, concomitantly acts as an antagonist on postsynaptic DA receptors. Moreover, the behavioural/biochemical profile seems to indicate a preferential limbic action for the (-)-enantiomer. Such an action could be explained on the basis of different feedback arrangements in the nigrostriatal and mesolimbic DA systems and it is suggested that compounds such as (-)-3-PPP may find future clinical application as "second-generation" antipsychotic agents, lacking in the debilitating motor side effects produced by drugs in current therapeutic use.
在寻找新型选择性多巴胺（DA）自受体激动剂的过程中，DA类似物3-(3-羟基苯基)-N-正丙基哌啶（3-PPP）被拆分为右旋（+）和左旋（-）对映体。通过行为学和生物化学方法对这些化合物进行了药理学评估。令人惊讶的是，（+）-和（-）-3-PPP对DA受体均显示出明确但不同的作用。因此，（+）-3-PPP是一种DA受体激动剂，对自受体和突触后受体均有活性，而（-）-3-PPP同样能激活DA自受体，但相反，它同时作为突触后DA受体的拮抗剂起作用。此外，行为学/生物化学特征似乎表明（-）-对映体具有优先的边缘系统作用。这种作用可以基于黑质纹状体和中脑边缘DA系统中不同的反馈机制来解释，并且有人提出，诸如（-）-3-PPP之类的化合物可能作为“第二代”抗精神病药物在未来找到临床应用，这类药物缺乏当前治疗中使用的药物所产生的使人衰弱的运动副作用。
