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在一项随机试验中,急性给予罗氟司特可增强健康年轻人类的感觉门控作用。

Acute administration of roflumilast enhances sensory gating in healthy young humans in a randomized trial.

机构信息

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6200 MD, Maastricht, The Netherlands.

Department of Neuropsychology and Psychopharmacology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.

出版信息

Psychopharmacology (Berl). 2018 Jan;235(1):301-308. doi: 10.1007/s00213-017-4770-y. Epub 2017 Nov 3.

Abstract

INTRODUCTION

Sensory gating is a process involved in early information processing which prevents overstimulation of higher cortical areas by filtering sensory information. Research has shown that the process of sensory gating is disrupted in patients suffering from clinical disorders including attention deficit hyper activity disorder, schizophrenia, and Alzheimer's disease. Phosphodiesterase (PDE) inhibitors have received an increased interest as a tool to improve cognitive performance in both animals and man, including sensory gating.

METHODS

The current study investigated the effects of the PDE4 inhibitor roflumilast in a sensory gating paradigm in 20 healthy young human volunteers (age range 18-30 years). We applied a placebo-controlled randomized cross-over design and tested three doses (100, 300, 1000 μg).

RESULTS

Results show that roflumilast improves sensory gating in healthy young human volunteers only at the 100-μg dose. The effective dose of 100 μg is five times lower than the clinically approved dose for the treatment of acute exacerbations in chronic obstructive pulmonary disease (COPD). No side-effects, such as nausea and emesis, were observed at this dose. This means roflumilast shows a beneficial effect on gating at a dose that had no adverse effects reported following single-dose administration in the present study.

CONCLUSION

The PDE4 inhibitor roflumilast has a favorable side-effect profile at a cognitively effective dose and could be considered as a treatment in disorders affected by disrupted sensory gating.

摘要

简介

感觉门控是一种涉及早期信息处理的过程,它通过过滤感觉信息来防止高皮质区域的过度刺激。研究表明,感觉门控过程在患有临床障碍的患者中受到干扰,包括注意力缺陷多动障碍、精神分裂症和阿尔茨海默病。磷酸二酯酶 (PDE) 抑制剂作为一种提高动物和人类认知表现的工具,包括感觉门控,引起了越来越多的关注。

方法

本研究在 20 名健康年轻的人类志愿者(年龄范围 18-30 岁)中,应用感觉门控范式研究了 PDE4 抑制剂罗氟司特的作用。我们采用安慰剂对照随机交叉设计,测试了三个剂量(100、300 和 1000μg)。

结果

结果表明,罗氟司特仅在 100μg 剂量下改善健康年轻人类志愿者的感觉门控。100μg 的有效剂量比治疗慢性阻塞性肺疾病(COPD)急性加重的临床批准剂量低五倍。在这个剂量下,没有观察到恶心和呕吐等副作用。这意味着罗氟司特在没有报告不良反应的单剂量给药后,在认知有效剂量下对门控产生有益的影响。

结论

PDE4 抑制剂罗氟司特在具有良好的认知效果的剂量下具有有利的副作用特征,可考虑用于受感觉门控障碍影响的疾病的治疗。

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