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SOLOMON H. SNYDER Receptor Research Reaches Neurology: Relevance to Neurodegenerative Diseases and Stroke President George Bush has heralded the 1990s as the decade of the brain, based largely on the rapid escalation of advances in the molecular neuro sciences and the likelihood that these will bear therapeutic fruit before the turn of the century. There is little doubt that the 1970s and 1980s have witnessed more remarkable advances in the molecular neurosciences than all of the preceding hundred years. Identification of receptor sites for drugs and neurotransmitters along with simple, sensitive, and specific means of monitoring them has made it possible to elucidate the mechanism of action for many known drugs and to identify new chemical entities as potential therapeutic agents. At the same time, the numbers of distinct neurotrans mitters have multiplied. Prior to 1970 only the biogenic amines were well accepted as transmitters. The early 1970s witnessed the gradual acceptance ofamino acids as major excitatory and inhibitory neurotransmitters. Identification of opiate receptors and the subsequent identification of the enkephalins as their endogenous ligands led to an appreciation of peptides as putative transmitters and the accumulation of as many as a hundred neuropeptides by the decade's end. In the 1980s the revolutions of molecular biology have been applied aggressively to the neurosciences with molecular cloning for neuropeptide precursors, many important neurochemical en zymes, and receptors for numerous transmitters.
List of contents
1. Preclinical Ischemia Model Systems.- 1. Primary Cultures for Testing Neuroprotective Drugs.- 2. Modeling Neurodegeneration and Neuroprotection in Hippocampal Slices.- 3. Stroke Models for Preclinical Trials of Neuroprotective Agents.- 4. Animal Models of Ischemia.- 5. Head Trauma Model Systems.- 2. Neuroprotective Approaches in Stroke and Head Trauma.- 6. Excitotoxicity, Cerebral Ischemia, and Neuroprotection by Competitive NMDA Receptor Antagonists.- 7. Excitatory Amino Acids and Neuroprotection.- 8. Calcium Channel Blockers and Neuroprotection.- 9. Self-Defense of the Brain: Adenosinergic Strategies in Neurodegeneration.- 10. Gangliosides: New Generation of Neuroprotective Agents.- 11. Lazaroids: Novel Cerebroprotective Antioxidants.- 12. Membrane-Derived Lipid Second Messengers as Targets for Neuroprotection: Platelet-Activating Factor.- 13. Protection Against Oxidative Damage to CNS by ?-Phenyl-tert-butyl Nitrone and Other Spin-Trapping Agents: A Novel Series of Nonlipid Free Radical Scavengers.- 14. Insulin, Hypoglycemia, and Ischemic Neuroprotection.- 15. Temperature Modulation of Neuronal Injury.- 3. Clinical Endpoints for Neuroprotective Drugs.- 16. Clinical Trial Issues in Stroke Therapy.- 17. Excitotoxicity and Neurodegenerative Disorders.
