Pathologically activated therapeutics for neuroprotection.
Many drugs that have been developed to treat neurodegenerative diseases fail to gain approval for clinical use because they are not well tolerated in humans. In this article, I describe a series of strategies for the development of neuroprotective therapeutics that are both effective and well tolerated. These strategies are based on the principle that drugs should be activated by the pathological state that they are intended to inhibit. This approach has already met with success, and has led to the development of the potentially neuroprotective drug memantine, an N-methyl-D-aspartate (NMDA)-type and glutamate receptor antagonist.
Lipton
Stuart A
SA
Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California at San Diego 10901 North Torrey Pines Road, La Jolla, California 29,037, USA. slipton@burnham.org
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008559:Memantine / Q000378:metabolism / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine