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Polyamines in the Brain: Distribution, Biological Interactions, and their Potential Therapeutic Role in Brain Ischaemia

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Abstract:

The endogenous polyamines (spermine, spermidine, and putrescine) are present at relatively high concentrations in the mammalian brain and play crucial roles in a variety of aspects of cell functioning. Stroke is the third most common cause of death and the leading cause of disability among adults in the western world. Brain polyamine levels change dramatically following cerebral ischaemia. Polyamines may be involved in the pathophysiological processes underlying brain ischaemia through several possible mechanisms. These include direct effects on ion channels and receptors modulating potassium, and most importantly calcium trafficking, or through the production of toxic metabolites. Considerable evidence shows that the noncompetitive polyamine antagonists, ifenprodil and eliprodil, are neuroprotective. Interestingly, novel polyamine analogues, such as N1-dansylspermine, BU36b, and BU43b, have also recently been shown to have neuroprotective potential. The exact mechanisms of the neuroprotection afforded by the polyamine antagonists and their clinical applicability is worthy of further study.

Keywords: CNS; NMDA; Polyamine; brain; neurotoxicity; stroke; therapeutics

Document Type: Research Article

DOI: https://doi.org/10.2174/092986707781058841

Affiliations: Department of Neurology,University of Connecticut Health Centre, 263 Farmington Avenue, Farmington, 06030 CT, USA.

Publication date: 2007-07-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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