Narcotic Drugs

I. The Chemistry of Narcotic Analgesic Drugs.- 1 The Structure of Narcotic Analgesic Drugs.- I. Introduction.- II. Morphine and Related Compounds.- III. Morphinan and Benzomorphan Derivatives.- IV. 4-Phenylpiperidines.- V. Diphenylpropylamines and Related Acyclic Analgesics.- VI. Miscellaneous Compounds.- VII. References.- 2 Methods of Chemical Analysis.- I. Introduction.- II. Solvent Extraction.- III. Qualitative Identification.- A. Chromatographic Methods.- B. Color Reactions.- C. Microcrystal Tests.- D. Physicochemical Methods.- E. Biological Methods.- IV. Quantitative Determination.- A. Photometric Methods.- B. Tracer Techniques.- C. Chromatographic Methods.- D. Polarography.- E. Titrimetric and Gravimetric Methods.- V. References.- 3 Structure-Activity Relationships.- I. Introduction.- A. Agonists, Antagonists, and Partial Agonists.- II. Morphine Analogs.- III. Morphinan Analogs.- IV. Benzomorphan Analogs.- V. Meperidine Analogs.- VI. Oripavine Derivatives.- VII. Miscellaneous.- VIII. Summary and Conclusions.- IX. References.- II. The Metabolic Disposition of Narcotic Analgesic Drugs.- 4 Physiological Disposition of Narcotic Agonists and Antagonists.- I. Introduction.- II. Dynamics of Drug Disposition.- A. Absorption.- B. Disposition.- C. Biotransformation.- D. Excretion.- III. Drug Disposition in the CNS.- A. Morphine.- B. Dihydromorphine.- C. Normorphine.- D. Heroin.- E. Codeine.- F. Meperidine.- G. Levorphanol.- H. Methadone.- I. Nalorphine.- J. Cyclazocine.- K. Pentazocine.- IV. Tolerance and Physical Dependence.- V. Summary.- VI. References.- 5 Transport in the Central Nervous System.- I. Introduction.- A. Concepts of Biological Transport.- B. Accumulation of Solutes in Cells and Tissues.- II. Transport in the Cerebrospinal Fluid System.- A. Isolated Choroid Plexus.- B. Ventriculo-Cisternal Perfusion.- III. Transport in Brain Tissue.- A. Cerebral Cortical Slices.- B. Homogenates of Brain.- C. Synaptosomes.- IV. References.- 6 Biotransformations.- I. Introduction.- II. General Patterns of Metabolism of Narcotic Drugs.- A. Chemical Reactions.- B. Effects of Species, Sex, and Dose.- C. Effects of Route of Administration.- III. Sites of Metabolism.- A. Liver.- B. Other Tissues.- IV. Metabolism of Individual Drugs.- A. d,l-a-Acetylmethadol.- B. Anileridine.- C. Codeine.- D. Cyclazocine.- E. Dextromethorphan.- F. Dihydromorphine.- G. Ethylmorphine.- H. Heroin.- I. Methadone.- J. Morphine.- K. Nalorphine.- L. Naloxone.- M. Normorphine.- N. Pentazocine.- O. d-Propoxyphene.- V. Metabolism in Tolerant Animals.- VI. References.- III. The Effects of Narcotic Analgesic Drugs on General Metabolic Systems.- 7 Intermediary and Energy Metabolism.- I. Introduction.- II. Effect of Narcotics In Vitro on Respiration and Glycolysis of Various Preparations of Brain.- III. Effect of Narcotics In Vitro on Stimulated Cerebral Cortical Slices.- IV. Effect of Morphine Administration on Cerebral Metabolism.- V. Effect of Narcotics on Certain Cerebral Enzymes In Vitro.- VI. Effect of Acute and Chronic Morphine Administration on Certain Cerebral Enzymes.- VII. Effect of Acute and Chronic Morphine Administration on Cerebral Glycolytic Intermediates.- VIII. Concluding Remarks.- IX. References.- 8 Phospholipid Metabolism.- I. Introduction.- II. Chemistry of Glycerides.- A. Neutral Glycerides.- B. Phosphoglycerides.- III. Biosynthesis of Glycerides.- A. Glyceride-Glycerol Intermediates.- B. Glycerophosphates.- C. Catabolism.- IV. Physiological Function of Glycerides.- A. Biological Membranes.- B. Active Transport.- C. Protein Synthesis.- D. Mitochondrial Function.- E. Phagocytosis.- V. Effect of Morphine and Nalorphine In Vitro and In Vivo.- A. In Vitro Studies.- B. In Vitro-In Vivo Studies.- VI. Subcellular Effect of Morphine In Vivo.- A. Brain.- B. Liver.- VII. Theoretical Considerations of Narcotic Drug Action.- A. Receptors—Phospholipids—Ions.- VIII. Summary.- IX. References.- 9 Protein and Nucleic Acid Metabolism.- I. Introduction.- II. Protein Metabolism.- A. Effects on Protein Metabolism in the Liver.- B. Effects on Protein Metabolism in Brain.- C. Amino Acids in Brain.- D. Inhibition of Protein Synthesis in Single Cells.- III. Nucleic Acid Metabolism.- A. Synthesis of RNA.- B. Synthesis of DNA.- C. Interactions of Narcotic Drugs with Nucleic Acids.- IV. Discussion.- V. References.- IV. The Effects of Narcotic Analgesic Drugs on Specific Systems.- 10 Catecholamines and 5-Hydroxytryptamine.- I. General Introduction.- II. Epinephrine.- A. Introduction.- B. Acute Effects of Morphine.- C. Effects of Chronic Morphinization.- D. Effects of Morphine Withdrawal.- E. Conclusions.- III. Norepinephrine.- A. Introduction.- B. Acute Effects of Morphine.- C. Chronic Morphinization.- D. Withdrawal of Morphine.- E. Conclusions.- IV. Dopamine.- A. Introduction.- B. Acute Effects of Morphine.- C. Chronic Effects of Morphine.- D. Effects of Morphine Withdrawal.- E. Conclusions.- V. 5-Hydroxytryptamine (5-HT, Serotonin).- A. Introduction.- B. Acute Effects of Morphine.- C. Chronic Effects of Morphine.- D. Effects of Morphine Withdrawal.- E. Conclusions.- VI. References.- 11 Acetylcholine and Cholinesterase.- I. The Effect of Morphine on Brain Acetycholine Levels.- II. The Effect of Morphine on Acetylcholinesterases.- A. In Vitro Studies.- B. In Vitro Studies.- III. The Effect of Morphine on Acetylcholine Synthesis.- IV. The Effect of Morphine on Acetylcholine Release.- V. Conclusions.- VI. References.- 12 Corticosteroid Hormones.- I. Introduction.- II. Steroid Biochemistry and Physiology.- A. Definitions and Terminology.- B. Control of Production.- III. Indexes of Adrenal Cortical Activity.- A. Adrenal Weights.- B. Circulating Eosinophil Counts.- C. Adrenal Ascorbic Acid Content.- D. Urinary and Plasma Steroids.- IV. Drug Effects.- A. Acute.- B. Chronic.- C. Abstinence.- D. Adrenal and Gonadal Responsivity.- E. Hydrocortisone Load Excretion.- F. In Vitro Steroid Synthesis.- G. Hormonal Control of Metabolism.- V. Morphine and the Adrenal Cortical Response to Various Stimuli.- VI. Summary.- VII. References.- 13 Hypothalamus: Anterior Pituitary Gland.- I. Introduction.- II. Neural Regulation of the Adenohypophysis.- III. Effects of Narcotic Analgesics on Anterior Pituitary Activity.- A. Adenocorticotropin (ACTH).- B. Thyrotropin (TSH).- C. Gonadotropins.- D. Growth Hormone (Somatotropin).- E. Prolactin.- IV. Summary and Conclusions.- V. References.- 14 Inorganic Ions: the Role of Calcium.- I. Introduction.- II. Antagonistic Effect of Calcium Ion on Morphine Analgesia.- III. Changes of Calcium Ion Level After Morphine.- IV. Calcium Concentration and the Inhibitory Effect of Morphine on the Respiration of Brain Slices In Vitro.- V. Flux of Cations Across the Cell Membrane.- VI. Lipid-Facilitated Transport of Ions.- VII. Effect of Calcium Ion on the Release of Biogenic Amines.- VIII. Effect of Calcium Ion on the Development of Tolerance.- IX. Conclusion.- X. References.- V. Sites of Action of Narcotic Analgesic Drugs.- 15 Single Cells.- I. Introduction.- II. Development of Tolerance and Physical Dependence in Tissue Culture.- III. Toxicity of Narcotics for Single Cells.- A. Mammalian Cells in Culture.- B. Microorganisms.- IV. Metabolic Studies.- A. In Bacteria.- B. In Other Systems.- V. Comments.- VI. References.- 16 The Nervous System.- I. Introduction.- II. The Isolated Spinal Cord.- A. Basic Neural Circuitry.- B. Alterations of Reflex Behavior.- C. Tolerance and Withdrawal.- III. The Decerebrated Neuraxis.- A. Cranial Nerves and Vital Centers.- B. Alterations of Lower Brainstem Functions.- C. Implications of Decerebration for Addiction.- IV. The Hypothalamus and Basal Ganglia.- A. Adaptive Processes.- B. Alterations of Subcortical Functions.- C. Implications of Decortication for Addiction.- V. The Whole Nervous System.- VI. Concluding Remarks.- VII. References.- 17 Kidney.- I. Introduction.- II. Antidiuretic Effect.- III. Development of Tolerance to the Antidiuretic Effect.- A. Explanation of Terms.- B. Studies in Rats.- C. Other Animals.- IV. Excretion of Narcotics and Metabolites in Urine.- A. Meperidine and Levorphanol Excretion and pH Dependence.- B. Morphine and Dihydromorphine Excretion.- V. References.- 18 In Peripheral Tissues.- I. The Action of Opiates on the Gastrointestinal Tract.- A. Gastrointestinal Effects of Opiates in Whole Animals.- B. Effects of Opiates in Isolated Intestinal Preparations.- II. The Action of Opiates on the Muscle of the Genitourinary Tract.- A. Urinary Tract.- B. Uterus.- III. The Effect of Opiates on the Rodent Lens.- A. The Nature of the Lens Opacity.- B. Production of Opacities in Isolated Lenses.- C. Influence of Respiratory Depression on the Production of Lens Opacities.- D. Role of Sympathetic Nervous System in the Lenticular Effect of Opiates.- E. Use of Lenticular Action of Opiates as a Model for Studying Drug-Receptor Interactions.- F. Tolerance to the Lenticular Effect of Opiates.- IV. References.- VI. Tolerance and Dependence.- 19 Tolerance and Physical Dependence.- I. The Riddle of Physical Dependence.- II. Criteria for Tolerance and Physical Dependence.- A. Tolerance.- B. Physical Dependence.- III. The Theoretical Link Between Narcotic Tolerance and Physical Dependence.- A. The Analogy to Enzyme Induction.- B. Consequences of the Induction Theory.- C. A Theory Based on Miscoding.- IV. Concluding Remarks.- V. References.- 20 Inhibitors of Tolerance Development.- I. Introduction.- II. Opioid Antagonists.- III. Effects of Biogenic Amine Depletors.- IV. Inhibitors of Protein Synthesis.- V. Other Inhibitors of Tolerance.- VI. Summary and Conclusions.- VII. References.- 21 Role of Possible Immune Mechanisms in the Development of Tolerance.- I. Introduction.- A. Theories of Tolerance.- II. Characteristics of the Development and Loss of Tolerance.- III. Possible Transferable Factors in Tolerant Animals.- A. Serum Factors.- B. Tissue Extracts.- IV. The Role of Interval and Dose in Tolerance Development.- V. The Effects of Immunosuppressors on Tolerance.- VI. Summary.- VII. References.- 22 Self-Administration Studies in Animals.- I. Introduction.- II. Techniques.- III. Suggested Biochemical Studies.- IV. References.- VII. Electrophysiological Studies in Man.- 23 Opiates and Antagonists.- I. Introduction.- II. Previous Studies.- III. Subjects and Methods.- IV. Observations.- A. Heroin.- B. Methadone.- C. Naloxone.- D. Cyclazocine.- E. Tybamate.- V. Discussion.- VI. Summary.- VII. References.- VIII. Pharmacologically Based Therapeutic Programs in Man.- 24 Opiate Antagonists in the Treatment of Heroin Dependence.- I. Introduction.- II. Cyclazocine.- A. Induction.- B. Heroin Challenge.- C. Secondary Effects.- D. Maintenance.- III. Naloxone.- A. Single Administration.- B. Chronic Oral Administration.- IV. Discussion.- V. Summary.- VI. References.- 25 Blockade with Methadone.- I. Introduction.- II. Clinical Results.- III. Pharmacology.- IV. Clinical Services.- V. Prospects for the Future.- VI. References.- 26 The Nalorphine (Pupil) Test in the Detection of Narcotic Use.- I. Introduction.- II. Measurement of Pupil Size.- III. Nalorphine Test.- IV. Naloxone Test.- V. Comparison with Urinalysis.- VI. References.