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Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders.

Youdim MB, Buccafusco JJ

Eve Topf and US National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research, Technion-Rappaport Faculty of Medicine and Department of Pharmacology, Haifa 31096, Israel. youdim@tx.technion.ac.il

Individuals with neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease are benefiting from drugs developed to act on a single molecular target. However, current pharmacological approaches are limited in their ability to modify significantly the course of the disease, and offer incomplete and transient benefit to patients. New therapeutic strategies comprise drug candidates designed specifically to act on multiple neural and biochemical targets for the treatment of cognition impairment, motor dysfunction, depression and neurodegeneration. Examples include the development of single molecular entities that combine two or more of the following properties: (i) cholinesterase inhibition; (ii) activation or inhibition of specific subtypes of acetylcholine receptors or alpha-adrenoceptors; (iii) anti-inflammatory activity; (iv) monoamine oxidase inhibition; (v) catechol-O-methyl transferase inhibition; (vi) nitric oxide production; (vii) neuroprotection; (viii) anti-apoptotic activity; and (ix) activation of mitochondrial-dependent cell-survival genes and proteins. These bi- or multi-functional compounds might provide greater symptomatic efficacy, and better utility as potential neuroprotective disease-modifying drugs.

Published 4 January 2005 in Trends Pharmacol Sci, 26(1): 27-35.
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