Glennon R A, Slusher R M, Lyon R A, Titeler M, McKenney J D
J Med Chem. 1986 Nov;29(11):2375-80. doi: 10.1021/jm00161a038.
Arylpiperazines, such as 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and its chloro analogue mCPP, are 5-HT1 agonists, whereas quipazine, i.e., 2-(1-piperazino)quinoline, appears to be a 5-HT2 agonist. Radioligand binding studies using rat cortical membrane homogenates and drug discrimination studies using rats trained to discriminate a 5-HT1 agonist (i.e., TFMPP) or a 5-HT2 agonist (i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM)) from saline reveal that quipazine and its 1-deaza analogue 2-naphthylpiperazine (2-NP) bind at 5-HT1 and 5-HT2 sites but produce stimulus effects similar to those of DOM. A structurally related compound, 1-naphthylpiperazine (1-NP), possesses a high affinity for 5-HT1 (Ki = 5 nM) and 5-HT2 (Ki = 18 nM) sites. 1-NP produces stimulus effects similar to those of TFMPP and is able to antagonize the stimulus effects produced by DOM. The present results suggest that the unsubstituted benzene ring of quipazine, and of its 1-deaza analogue 2-naphthylpiperazine, makes a significant contribution to the binding of these agents to 5-HT2 sites and, more importantly, may account for their 5-HT2 agonist properties.
芳基哌嗪类化合物，如1-（3-三氟甲基苯基）哌嗪（TFMPP）及其氯代类似物mCPP，是5-羟色胺1（5-HT1）激动剂，而喹哌嗪，即2-（1-哌嗪基）喹啉，似乎是一种5-羟色胺2（5-HT2）激动剂。使用大鼠皮层膜匀浆进行的放射性配体结合研究以及使用经训练以区分5-HT1激动剂（即TFMPP）或5-HT2激动剂（即1-（2,5-二甲氧基-4-甲基苯基）-2-氨基丙烷（DOM））与生理盐水的大鼠进行的药物辨别研究表明，喹哌嗪及其1-脱氮类似物2-萘基哌嗪（2-NP）在5-HT1和5-HT2位点结合，但产生的刺激效应与DOM相似。一种结构相关的化合物，1-萘基哌嗪（1-NP），对5-HT1（Ki = 5 nM）和5-HT2（Ki = 18 nM）位点具有高亲和力。1-NP产生的刺激效应与TFMPP相似，并且能够拮抗DOM产生的刺激效应。目前的结果表明，喹哌嗪及其1-脱氮类似物2-萘基哌嗪的未取代苯环对这些药物与5-HT2位点的结合有重要贡献，更重要的是，可能解释了它们的5-HT2激动剂特性。
