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

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.

Neuroprotective strategies and the underlying molecular basis of cerebrovascular stroke

“…130 Citicoline is in clinical use in a number of countries, including Argentina, Austria, Chile, Indonesia, Mexico, Portugal, Thailand, and Venezuela. 18 …”

“…51 As is apparent, various limitations in study design and translation of preclinical findings to clinical trials have affected these trials. 18 Time to treatment is an important and difficult feature to control, but must be considered when translating laboratory findings to human trials. Adequate preclinical data to support larger clinical trials have also been lacking in some cases, including objective outcomes evaluating improvement in infarct size and neurobehavioral function, in addition to other trial design features.…”

Potential of Anthocyanin From Purple Sweet Potato (Ipomoea batatas) To Increase BDNF Level and VEGF Expression in The Cerebellum of Ischemic Stroke Rats

“…Neuroprotective action acts in the increase of phosphatidylcholine synthesis, stimulation of glutathione synthesis, and reduce arachidonic acid levels formed after ischemic stroke [10]. Anthocyanin is expected to be able to decrease the cytotoxicity, calcium dysregulation, mitochondrial dysfunction, oxidative and nitrosative stress and inflammation.…”

“…Anthocyanin is expected to be able to decrease the cytotoxicity, calcium dysregulation, mitochondrial dysfunction, oxidative and nitrosative stress and inflammation. In addition, anthocyanin acts to reduce tissue acidosis, blood-brain barrier, brain neuron apoptosis, necrosis and autophagy [10].…”

“…Recent studies have shown that anthocyanin from purple sweet potato inhibits inflammation response in rat brain induced lipopolysaccharide by blocking of signaling pathways in Extracellular Signal-Regulated Kinase (ERK), The C-Jun N-Terminal Kinase (JNK) and Nuclear Factor Kappa-B (Nf-kB) signaling [9]. As flavonoids derivative, anthocyanin has been predicted to maintain the fragility of capillaries to protect the brain from injury [10]. Thus, due to its biological activities, anthocyanin from purple sweet potato could be used as a therapeutic agent in brain ischemic stroke.…”