M4 agonists/5HT7 antagonists with potential as antischizophrenic drugs: Serominic compounds
详细信息 查看全文
- 作者：Colin J. Suckling ; John A. Murphy ; Abedawn I. Khalaf ; Sheng-ze Zhou ; Dimitris E. Lizos ; Albert Nguyen van Nhien ; Hiroshi Yasumatsu ; Allan McVie ; Louise C. Young ; Corinna McCraw ; <i>et al.i>
- 关键词：Anti-schizophrenic ; M4 receptor agonist ; 5HT7 receptor antagonist ; Tetrahydroisoquinolines ; Amidines
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 出版时间：1 May 2007
- 年：2007
- 卷：17
- 期：9
- 页码：2649-2655
- 全文大小：389 K
文摘
Chronic low-dose treatment of rats with the psychomimetic drug, phencyclidine, induces regionally specific metabolic and neurochemical changes in the CNS that mirror those observed in the brains of schizophrenic patients. Recent evidence suggests that drugs targeting serotoninergic and muscarinic receptors, and in particular 5-HT7 antagonists and M4 agonists, exert beneficial effects in this model of schizophrenia. Compounds that display this combined pattern of activity we refer to as <i>serominici> compounds. Based upon leads from natural product screening, we have designed and synthesised such serominic compounds, which are principally arylamidine derivatives of tetrahydroisoquinolines, and shown that they have the required serominic profile in ligand binding assays and show potential antipsychotic activity in functional assays.