Cholinergic muscarinic M1 and M4 receptors as therapeutic targets for cognitive, behavioural, and psychological symptoms in psychiatric and neurological disorders

被引：43

作者：

Erskine, Daniel ^{[1
]}

Taylor, John-Paul ^{[1
]}

Bakker, Geor ^{[2
]}

Brown, Alastair J. H. ^{[2
]}

Tasker, Tim ^{[2
]}

Nathan, Pradeep J. ^{[2
,3
,4
]}

机构：

[1] Newcastle Univ, Inst Neurosci, Newcastle, England

[2] Sosei Heptares, Cambridge, England

[3] Univ Cambridge, Dept Psychiat, Cambridge, England

[4] Monash Univ, Sch Psychol Sci, Melbourne, Vic, Australia

来源：

DRUG DISCOVERY TODAY | 2019年 / 24卷 / 12期

关键词：

ACETYLCHOLINE-RECEPTOR; LEWY BODIES; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; BASAL FOREBRAIN; M1; RECEPTORS; DEMENTIA; SCHIZOPHRENIA; BINDING;

D O I：

10.1016/j.drudis.2019.08.009

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Cholinergic dysfunction is involved in a range of neurological and psychiatric disorders, including schizophrenia, dementia and Lewy body disease (LBD), leading to widespread use of cholinergic therapies. However, such drugs have focused on increasing the availability of acetylcholine (ACh) generally, with relatively little work done on the muscarinic system and specific muscarinic receptor subtypes. In this review, we provide an overview of the major cholinergic pathways and cholinergic muscarinic receptors in the human brain and evidence for their dysfunction in several neurological and psychiatric disorders. We discuss how the selectivity of cholinergic system dysfunction suggests that targeted cholinergic therapeutics to the muscarinic receptor subtypes will be vital in treating several disorders associated with cognitive dysfunction and behavioural and psychological symptoms.

引用

页码：2307 / 2314

页数：8

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