Neuroprotective drug

Knowledge of the health of the cells after a stroke is fundamental if the cells are still alive, the use of neuroprotectant drugs can be useful to minimise brain damage otherwise, their utilisation is useless. A chemical parameter capable of assessing the state of health of tissue cells is pH. In fact, the death of tissue cells is followed by formation of lactic acid, which causes a decrease in blood pH. Normal values are around 7.4 a decrease below this value in the region in which a stroke has taken place is an index of the death of cells. 

An important class of noncompetitive antagonists selective for AMPA receptors is represented by the 2,3-benzodiazepines such as GYKI 53655. These compounds act at sites different from those acted on by cyclothiazide and are useful tools for isolating synaptic responses mediated by kainate receptors. These compounds also show some promise as neuroprotective drugs for treating ischemic neuronal injury. 

In this contribution we want to provide a short overview addressing the current state-of-the-art of water-soluble fullerene derivatives and their potential applications as antioxidant or neuroprotective drug candidates. After summarizing the most prominent concepts of designing water-soluble fullerenes in the first chapter we will present some more recent achievements with respect to biological activities of antioxidant fullerenes, with emphasis on our own results. 

Bruno V, Battaglia G, Copani A, et al (2001) Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs. J Cereb Blood FlowMetab 21 1013-1033 Bryson HM, Fulton B, Benfield P (1996) Riluzole—a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in amyotrophic lateral sclerosis. Drugs 52 549-563... 

It is important to note that MRI selection of patients does not just apply to thrombolytic trials. In fact, selecting patients with an ischaemic penumbra may be critically important for trials of neuroprotective drugs, and other therapies such as manip-... 

By using a thresholding approach in a 3-D CBF data set, we could show that 54% of the total ischemic lesion volume could be attributed to the penumbra, only 46% to the infarct core at 1.5 h post MCA occlusion (Back et al. 1995). Those areas with pending infarction show potentially reversible changes that can be addressed by therapeutic interventions like recanalizing therapy and/or neuroprotective drugs. 

Authors Year Neuroprotective drug Species Animal model Result... 

Metabolic effects of hypothermia on neuroprotective drug pharmacokinetics... 

The efficacy and safety of clomethiazole (75 mg/kg by intravenous infusion over 24 hours), as a neuroprotective drug, were studied in a double-blind, placebo-controlled trial (CLASS, the Clomethiazole Acute Stroke Study) in 1360 patients with acute hemispheric stroke (4). Clomethiazole was generally well tolerated and safe. Sedation was the most common adverse event, leading to treatment withdrawal in 16% of patients compared with 4.2% of placebo-treated patients. 

B6 peptide was discovered as a substitute for transferrin, and was conjugated with PEG-PLA nanoparticles (NP) with the aim of enhancing the delivery of neuroprotective drugs across the BBB for the treatment of AD. B6-modified NP (B6-NP) exhibited significantly higher accumulation in brain capillary endothelial cells via lipid raft-mediated and clathrin-mediated endocytosis. Administration of B6-NP encapsulated neuroprotective peptide— NAPVSIPQ (NAP)—to AD mouse models showed amelioration in learning impairments, cholinergic disruption, and loss of hippocampal neurons [604],... 

Jayakar, S.S. and Dikshit, M., 2004. AMPA receptor regulation mechanisms future target for safe neuroprotective drugs, Int. J. Neurosci., 114, pp. 695-734. 

Lumley, L.A., C.L. Robison, LY. Nwaneri, et al. 2005. Behavioral and physiological effects of the nerve agent VX in rats model for assessment of neuroprotective drugs. Society for Neuroscience conference, Washington, DC, Prog. No. 337.14. 

In conclusion, the future of neuroprotectant drug delivery is exciting. Multiple targets have been identified, and novel, sustained delivery systems are under development. Difficulties remain, many at the cellular level, in better defining the selective vulnerabilities and requirements of specific populations of neurons. Nevertheless, it is likely that more selective neuroprotectants will someday be added to the therapeutic arsenal. 

Neuroprotective drugs may have a role in increasing the efficacy and safety of thrombolysis. Because the risk... 

De Kreyser, J., Suiter, G., and Luiten, R G. (1999). Clinical trials with neuroprotective drugs in acute ischaemic stroke are we doing the right thing Trends Neurosci 22, 535-540. 

Tredici G, Miloso M, Nicolini G, Galbiati S, Cavaletti G, BerteUi A. Resveratrol, map kinases and neuronal cells might wine be a neuroprotectant. Drugs Exp Clin Res 1999 25 99-103. 

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