Allosteric activators of muscarinic receptors as novel approaches for treatment of CNS disorders

被引：57

作者：

Digby, Gregory J. ^{[1
]}

Shirey, Jana K. ^{[2
]}

Conn, P. Jeffrey ^{[3
]}

机构：

[1] Vanderbilt Univ, Dr Jeff Conns Lab, Nashville, TN USA

[2] Vanderbilt Univ, Dr Maureen Hahns Lab, Nashville, TN USA

[3] Vanderbilt Program Drug Discovery, Nashville, TN USA

来源：

MOLECULAR BIOSYSTEMS | 2010年 / 6卷 / 08期

关键词：

PROTEIN-COUPLED RECEPTORS; SUBTYPE-SPECIFIC ANTIBODIES; BASAL FOREBRAIN LESIONS; ACETYLCHOLINE-RECEPTOR; ALZHEIMERS-DISEASE; NUCLEUS BASALIS; SCANNING MUTAGENESIS; AGONIST XANOMELINE; PREFRONTAL CORTEX; M-1; RECEPTOR;

D O I：

10.1039/c002938f

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Muscarinic acetylcholine receptors (mAChRs) represent exciting therapeutic targets for the treatment of multiple CNS disorders. The high degree of conservation of amino acids comprising the orthosteric acetylcholine (ACh) binding site between individual mAChR subtypes has hindered the development of subtype-selective compounds that bind to this site. As a result, many academic and industry researchers are now focusing on developing allosteric activators of mAChRs including both positive allosteric modulators (PAMs) and allosteric agonists. In the past 10 years major advances have been achieved in the discovery of allosteric ligands that possess much greater selectivity for individual mAChR subtypes when compared to previously developed orthosteric agents. These novel allosteric modulators of mAChRs may provide therapeutic potential for treatment of a number of CNS disorders such as Alzheimer's disease and schizophrenia.

引用

页码：1345 / 1354

页数：10

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