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体内脑微透析:神经精神药理学与药物发现的进展

In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery.

作者信息

Darvesh Altaf S, Carroll Richard T, Geldenhuys Werner J, Gudelsky Gary A, Klein Jochen, Meshul Charles K, Van der Schyf Cornelis J

机构信息

Pharmaceutical Sciences-Neurotherapeutics Focus Group, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272, USA.

出版信息

Expert Opin Drug Discov. 2011 Feb;6(2):109-127. doi: 10.1517/17460441.2011.547189.

DOI:10.1517/17460441.2011.547189
PMID:21532928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3083031/
Abstract

INTRODUCTION

Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo microdialysis technique allows measurement of neurotransmitters such as acetycholine (ACh), the biogenic amines including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), amino acids such as glutamate (Glu) and gamma aminobutyric acid (GABA), as well as the metabolites of the aforementioned neurotransmitters, and neuropeptides in neuronal extracellular fluid in discrete brain regions of laboratory animals such as rodents and non-human primates. AREAS COVERED: In this review we present a brief overview of the principles and procedures related to in vivo microdialysis and detail the use of this technique in the pre-clinical measurement of drugs designed to be used in the treatment of chemical addiction, neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and as well as psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. This review offers insight into the tremendous utility and versatility of this technique in pursuing neuropharmacological investigations as well its significant potential in rational drug discovery. EXPERT OPINION: In vivo microdialysis is an extremely versatile technique, routinely used in the neuropharmacological investigation of drugs used for the treatment of neurological disorders. This technique has been a boon in the elucidation of the neurochemical profile and mechanism of action of several classes of drugs especially their effects on neurotransmitter systems. The exploitation and development of this technique for drug discovery in the near future will enable investigational new drug candidates to be rapidly moved into the clinical trial stages and to market thus providing new successful therapies for neurological diseases that are currently in demand.

摘要

引言

微透析是一种重要的体内采样技术,可用于细胞外组织液的分析。该技术在临床前和临床均有应用,但在神经科学中应用最为广泛。体内微透析技术能够测量神经递质,如乙酰胆碱(ACh)、生物胺,包括多巴胺(DA)、去甲肾上腺素(NE)和5-羟色胺(5-HT),氨基酸,如谷氨酸(Glu)和γ-氨基丁酸(GABA),以及上述神经递质的代谢产物,还有实验动物(如啮齿动物和非人类灵长类动物)离散脑区神经元细胞外液中的神经肽。

涵盖领域

在本综述中,我们简要概述了与体内微透析相关的原理和程序,并详细介绍了该技术在临床前测量用于治疗化学成瘾、神经退行性疾病(如阿尔茨海默病(AD)、帕金森病(PD))以及精神疾病(如注意力缺陷多动障碍(ADHD)和精神分裂症)的药物中的应用。本综述深入探讨了该技术在神经药理学研究中的巨大实用性和多功能性,以及其在合理药物发现中的巨大潜力。

专家观点

体内微透析是一种极其通用的技术,常用于治疗神经系统疾病药物的神经药理学研究。该技术在阐明几类药物的神经化学特征和作用机制,特别是它们对神经递质系统的影响方面发挥了重要作用。在不久的将来,利用和开发该技术进行药物发现将使研究性新药候选物能够迅速进入临床试验阶段并上市,从而为目前急需的神经系统疾病提供新的成功治疗方法。