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Review
. 2016 Nov;6(6):522-530.
doi: 10.1016/j.apsb.2016.06.013. Epub 2016 Jul 28.

The fate of medications evaluated for ischemic stroke pharmacotherapy over the period 1995-2015

Xiaoling Chen  1 , Kewei Wang  2
Affiliations
Review

The fate of medications evaluated for ischemic stroke pharmacotherapy over the period 1995-2015

Xiaoling Chen et al. Acta Pharm Sin B. 2016 Nov.

Abstract

Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis using recombinant tissue plasminogen activators (rt-PAs) to breakdown blood clots. Neuroprotective agents that inhibit excitatory neurotransmitters are also used to treat ischemic stroke but have failed to translate into clinical benefits. This poses a major challenge in biomedical research to understand what causes the progressive brain cell death after stroke and how to develop an effective pharmacotherapy for stroke. This brief review analyzes the fate of about 430 potentially useful stroke medications over the period 1995-2015 and describes in detail those that successfully reached the market. Hopefully, the information from this analysis will shed light on how future stroke research can improve stroke drug discovery.

Keywords: ADP, adenosine diphosphate; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ASIC1a, acid-sensing ion channel 1a; BDNF, brain-derived neurotrophic factor; CFDA, the China Food and Drug Administration; CNTF, ciliary neurotrophic factor; GDNF, glial cell line–derived neurotrophic factor; Ion channel; Ischemic stroke; MHRA, Medicine and Healthcare Products Regulatory Agency; NBP, butylphthalide/3-n-butylphthalide; NGF, nerve growth factor; NMDA, N-methyl-D-aspartate; Neuroprotective agent; Non-NMDA mechanism; TCM, traditional Chinese medicine; TRP, transient receptor potential; TRPC, transient receptor potential canonical; TRPM, transient receptor potential melastatin; TRPV, transient receptor potential vanilloid; Thrombosis; Traditional Chinese medicine; iGluRs, ionotropic glutamate receptors; rt-Pas, recombinant tissue plasminogen activators.

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Figures

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Graphical abstract
Fig. 1
Figure 1
The landscape of ischemic stroke drug discovery and therapy over the period 1995–2015. (A) The classification of 430 drug candidates by pie chart based on the mechanism of action: (B) the 4% of drugs on the market; (C) the 9% undergoing clinical trials; (D) the 17% undergoing preclinical evaluation and (E) the 70% of failed drug candidates.
See this image and copyright information in PMC

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