Scott M K, Martin G E, DiStefano D L, Fedde C L, Kukla M J, Barrett D L, Baldy W J, Elgin R J, Kesslick J M, Mathiasen J R
Department of Biological Research, McNeil Pharmaceutical, R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477.
J Med Chem. 1992 Feb 7;35(3):552-8. doi: 10.1021/jm00081a018.
Recently, we reported on a series of arylpiperazines 4 which exhibit high affinity for the serotonin 5-HT-1A and 5-HT-1B binding sites. Although these compounds interact weakly with dopamine D-1 and D-2 receptors, they are reasonably potent in inhibiting conditioned avoidance responding (CAR) in the rat, an indication of potential antipsychotic activity. Conversion of these arylpiperazines to pyrrole Mannich bases has provided a series of compounds (10-44) which exhibit potent inhibition of CAR when given po and have strong affinity for both the D-2 and 5-HT-1A binding sites. Some of these agents also fail to produce catalepsy. The D-2 binding data and the block of CAR suggest that they are potential antipsychotic agents and the lack of cataleptogenic potential suggests some might possess less liability for producing extrapyramidal side effects and tardive dyskinesias in man.
最近，我们报道了一系列对血清素5-HT-1A和5-HT-1B结合位点具有高亲和力的芳基哌嗪4。尽管这些化合物与多巴胺D-1和D-2受体的相互作用较弱，但它们在抑制大鼠条件性回避反应（CAR）方面相当有效，这表明它们具有潜在的抗精神病活性。将这些芳基哌嗪转化为吡咯曼尼希碱得到了一系列化合物（10-44），这些化合物口服给药时对CAR具有强效抑制作用，并且对D-2和5-HT-1A结合位点都具有很强的亲和力。其中一些药物也不会产生僵住症。D-2结合数据和对CAR的阻断表明它们是潜在的抗精神病药物，而缺乏致僵住症的潜力表明其中一些药物在人类中产生锥体外系副作用和迟发性运动障碍的可能性较小。
