A Neurotoxins.- 1 Isoquinoline Derivatives.- 1. Introduction.- 2. Tetrahydroisoquinoline (TIQ).- 2.1 Presence of TIQ in nature and in food.- 2.2 Methods for identification and measurement of TIQ.- 2.3 Presence of TIQ in tissues.- 2.4 Endogenous synthesis of TIQ.- 2.5 Parkinsonism caused by TIQ.- 2.6 Metabolism of TIQ in the brain.- 3. 1,2-Dihydroisoquinoline.- 4. 4-Hydroxy-TIQ.- 5. 1-Benzyl-TIQ.- 6. 1-Phenyl-N-methyl-TIQ and 1-phenyl-TIQ.- 7. Salsolinol (SAL).- 7.1 Presence of SAL in tissues, body fluids, food, and nature.- 7.2 Biosynthetic pathway of SAL.- 7.3 Neurotoxicity of SAL.- 7.4 Metabolism of SAL.- 8. Norsalsolinol.- 9. N-Methyl-salsolinol and N-methyl-norsalsolinol.- 10. 1,2,3,4-Tetrahydro-2-methyl-4,6,7-i soquinolinetriol.- 11. Methods for identification and measurement of catecholic TIQs.- 12. The sites of toxicological activity.- 12.1 Inhibition of mitochondrial respiratory enzymes.- 12.2 Hydroxyl radical formation.- 2 TIQ Derivatives in the Human Central Nervous System.- 1. History of the Presence of TIQ derivatives.- 2. Analytical Methods.- 2.1 Cerebrospinal Fluid (CSF).- 2.1.1 Lumbar Puncture.- 2.1.2 High Performance Liquid Chromatography.- 2.2 Urine.- 2.2.1 Urine measurements of Salsolinol.- 2.2.2 Affinity chromatography.- 2.2.3 High Performance Liquid Chromatography.- 3. Frequency and TIQ Levels measured by HPLC-ECD.- 3.1 N-Methyl-norsalsolinol.- 3.2 Salsolinol.- 4. TIQ Derivatives and Dopamine Metabolites.- 5. Stereospecifity and Enantiomeric Separation.- 6. Cerebral Lesions by TIQ Derivatives.- 6.1 TIQ, 1-Methyl-TIQ, 2-Methyl-TIQ.- 6.2 N-Methyl-[R]-salsolinol.- 6.3 N-Methyl-norsalsolinol.- 6.4 N-Methyl-4-hydroxy-norsalsolinol.- 7. Hallucinosis and TIQ Derivatives.- 3 Animal Model of Parkinson's Disease Prepared by N-Methyl-R-Salsolinol.- 1. MPTP and N-Methylation.- 2. Preparation of a rat model of Parkinson's disease.- 2.1 Materials.- 2.2 Animal experiments.- 3. Behavior observation.- 3.1 Behavior changes due to perturbation in dopaminergic system.- 4. Biochemical analysis in the brain.- 4.1 Methods.- 4.2 Quantitative analyses of monoamines, their metabolites and isoquinolines.- 4.3 Enantiomeric analysis of salsolinol derivatives.- 4.4 Assay of tyrosine hydroxylase activity.- 4.5 Biochemical changes by infusion of N-methyl-[R]-salsolinol and DMDHIQ+.- 4.6 Changes of monoamines and their metabolites.- 4.7 Accumulation of N-methyl-[R]-salsolinol and DMDHIQ+.- 4.8 Reduction of tyrosine hydroxylase activity.- 5. Histological study.- 5.1 Methods for histological analysis.- 5.2 Cytotoxicity in the striatum.- 5.3 Depletion of dopamine neurons in the substantia nigra.- 6. Discussion.- 4 Putative Endogenous Neurotoxins Derived from the Biogenic Amine Neurotransmitters.- 1. Introduction.- 2. Alzheimer's disease.- 3. Ischemia-Reperfusion.- 4. Methamphetamine.- 5. In vitro oxidation chemistry of the biogenic amine neurotransmitter.- 5.1 In vitro oxidation chemistry of 5-hydroxytryptamine.- 5.2 In vitro oxidation chemistry of dopamine.- 5.3 In vitro oxidation chemistry of norepinephrine.- 6. In vivo oxidation chemistry of the biogenic amine neurotransmitter.- 6.1 In vivo oxidation of 5-hydroxytryptamine.- 6.2 In vivo oxidation of dopamine and norepinephrine.- 7. Properties of putative aberrant oxidative metabolites of the biogenic amine neurotransmitters.- 7.1 Redox properties of putative aberrant oxidative metabolites of 5-HT and 5-HTPP.- 7.2 Redox properties of putative aberrant oxidative metabolites of DA and NE.- 8. Neurochemical and neurobiological properties of putative aberrant oxidative metabolites of 5-HT, DA and NE.- 9. Serotonin binding proteins.- 10. Discussion.- 11. Summary.- 5 ?-Carboline Derivatives as Neurotoxins.- 1. Biosynthetic and organic synthetic routes to TH?C's and ?C's.- 2. Overview of the effects of ?C's and their metabolic derivatives on the nervous system.- 3. Measurement and analysis of TH?C's, ?C's and their derivatives.- 4. Enzymatic formation of N-methylated ?C cations from nonpolar ?
It is a great pleasure to write the foreword to this important volume for several reasons. First: As far as we know, already primitive societies had to cope with environmental toxins of many kinds and set up regulations to limit their effects on food and drug use. Modem science, synthesizing tens of millions of new compounds has incredibly magnified this challenge. Today, xenobiotic metabolism has become a crucial task for humans and many other species alike. Second: When reading this book, one is impressed by the extraordinary speed at which neurotoxicology has advanced. Obviously, processing (and endogenous formation) oftox ins has become an extremely relevant topic. When I had the chance, almost three decades ago, to work in chemical pharmacology with Bernard B. Brodie at NIH, the drug metabo lizing system of the liver had just been recognized and characterized. We had just started to work on the biogenic amines, newly discovered cyclic nucleotides in rat brain, human cere brospinal fluid, and on the effects of toxic drugs like amphetamines. Today, biochemical neuropharmacology is a mature field of neuroscience.
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