The challenges of modulating the 'rest and digest' system: acetylcholine receptors as drug targets.
The challenges of modulating the 'rest and digest' system: acetylcholine receptors as drug targets.
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DOI：
10.1016/j.drudis.2016.09.011
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发表时间：
2017
影响因子：
7.4
通讯作者：
S. VanPatten;Y. Al-Abed
中科院分区：
文献类型：
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作者：
S. VanPatten;Y. Al-Abed
乙酰胆碱系统在自主神经系统中起着重要作用。乙酰胆碱受体是许多临床批准的药物的靶点。受体亚型特异性可以影响下游效应的调节。调节水平调节乙酰胆碱系统以适应现有的生物条件。这种复杂的调节必须在配体设计中考虑。乙酰胆碱是副交感神经和交感神经系统的主要神经递质，在20世纪初被发现。多年来，研究人员已经揭示了许多关于其调节，其受体的特性以及影响其终末效应的下游信号传导的特征。乙酰胆碱系统，传统上与神经肌肉通讯有关，现在已知在免疫系统的调节和其他“休息和消化”作用中起着至关重要的作用。最近的研究试图阐明该系统在大脑功能中的作用，包括认知，睡眠，唤醒，动机，奖励和疼痛。我们强调临床批准和实验药物，调节乙酰胆碱受体。靶向乙酰胆碱受体的复杂性是巨大的，寻找与特定乙酰胆碱受体相关的药物开发的未来适应症仍然是一个挑战。
HighlightsThe acetylcholine system has a major role in the autonomic nervous system.Acetylcholine receptors are targets for many clinically approved drugs.Receptor subtype specificity can influence which downstream effects are modulated.Levels of regulation tune the acetylcholine system to existing biologic conditions.This intricate regulation must be taken into consideration in ligand design.Acetylcholine, a major neurotransmitter of the parasympathetic and sympathetic nervous systems, was discovered in the early 1900s. Over the years, researchers have revealed much about its regulation, properties of its receptors and features of the downstream signaling that influence its terminal effects. The acetylcholine system, traditionally associated with neuromuscular communication, is now known to play a crucial part in modulation of the immune system and other ‘rest and digest’effects. Recent research seeks to elucidate the system's role in brain functions including cognition, sleep, arousal, motivation, reward and pain. We highlight clinically approved and experimental drugs that modulate the acetylcholine receptors. The complexities in targeting the acetylcholine receptors are vast and finding future indications for drug development associated with specific acetylcholine receptors remains a challenge.