Muscarinic acetylcholine receptors as CNS drug targets

被引：329

作者：

Langmead, Christopher J. ^{[1
]}

Watson, Jeannette ^{[1
]}

Reavill, Charlie ^{[1
]}

机构：

[1] GlaxoSmithKline, Psychiat Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

来源：

PHARMACOLOGY & THERAPEUTICS | 2008年 / 117卷 / 02期

关键词：

muscarinic receptors; mAChR; CNS; Alzheimer's disease; schizophrenia; Parkinson's disease; drug dependence;

D O I：

10.1016/j.pharmthera.2007.09.009

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the CNS where they control a variety of neuronal functions. Due to their roles in a number of CNS processes, mAChRs have long been a target of the drug discovery industry; however, the only mAChR ligands approved for use in the clinic are non-selective antagonists for the treatment of Parkinson's disease. This article briefly reviews recent progress made in mAChR drug discovery for Alzheimer's disease (AD), schizophrenia and Parkinson's disease, with particular emphasis on novel target validation, as well as highlighting novel indications such as drug addiction. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：232 / 243

页数：12

共 118 条

[61] Loss of anti-cataleptic effect of scopolamine in mice lacking muscarinic acetylcholine receptor subtype 4 [J].

Karasawa, H ;

Taketo, MM ;

Matsui, M .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2003, 468 (01) :15-19

[62]

KATZENSCHLAGER R, 2006, COCHRANE DATABASE SY, V3

[63] CLINICAL, PATHOLOGICAL, AND NEUROCHEMICAL CHANGES IN DEMENTIA - A SUBGROUP WITH PRESERVED MENTAL STATUS AND NUMEROUS NEOCORTICAL PLAQUES [J].

KATZMAN, R ;

TERRY, R ;

DETERESA, R ;

BROWN, T ;

DAVIES, P ;

FULD, P ;

XIONG, RB ;

PECK, A .

ANNALS OF NEUROLOGY, 1988, 23 (02) :138-144

[64] Neuroscience of addiction [J].

Koob, GF ;

Sanna, PP ;

Bloom, FE .

NEURON, 1998, 21 (03) :467-476

[65] Reduced high-affinity agonist binding at the M1 muscarinic receptor in Alzheimer's disease brain:: Differential sensitivity to agonists and divalent cations [J].

Ladner, CJ ;

Lee, JM .

EXPERIMENTAL NEUROLOGY, 1999, 158 (02) :451-458

[66]

Lai MKP, 2001, NEUROLOGY, V57, P805

[67] Probing the molecular mechanism of interaction between 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the muscarinic M1 receptor:: Direct pharmacological evidence that AC-42 is an allosteric agonist [J].

Langmead, CJ ;

Fry, VAH ;

Forbes, IT ;

Branch, CL ;

Christopoulos, A ;

Wood, MD ;

Herdon, HJ .

MOLECULAR PHARMACOLOGY, 2006, 69 (01) :236-246

[68] Mechanism of action of antipsychotic drugs:: From dopamine D2 receptor antagonism to glutamate NMDA facilitation [J].

Laruelle, M ;

Frankle, WG ;

Narendran, R ;

Kegeles, LS ;

Abi-Dargham, A .

CLINICAL THERAPEUTICS, 2005, 27 :S16-S24

[69] Alternatives to levodopa in the initial treatment of early Parkinson's disease [J].

Lees, A .

DRUGS & AGING, 2005, 22 (09) :731-740

[70]

LEVEY AI, 1991, J NEUROSCI, V11, P3218

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