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5-Hydroxytryptamine and Related Indolealkylamines: Handbook of Experimental Pharmacology, cartea 19

Editat de Vittorio Erspamer
en Limba Engleză Paperback – 18 apr 2012

Din seria Handbook of Experimental Pharmacology

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Specificații

ISBN-13: 9783642854699
ISBN-10: 3642854699
Pagini: 952
Ilustrații: XX, 928 p.
Dimensiuni: 170 x 244 x 50 mm
Greutate: 1.48 kg
Ediția:Softcover reprint of the original 1st ed. 1966
Editura: Springer Berlin, Heidelberg
Colecția Springer
Seria Handbook of Experimental Pharmacology

Locul publicării:Berlin, Heidelberg, Germany

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Cuprins

1. Histology of the enteroehromaffin cell system.- I. Introduction.- II. The elements of the enterochromaffin cell system.- III. Histochemical characteristics of 5-HT of diagnostic importance.- A. Fixability characteristic.- B. Colour reaction.- 1. Chromaffin reactio.- 2. Argentaffin reactions and argentophil.- 3. Diazo reaction.- 4. Pearse’s thyo-indoxyl reaction.- 5. Other reactions.- 6. Reactions which do not give the expected positive response.- 7. Various procedures.- C. Fluorescence as a diagnostic criterion.- D. Limits of histochemical diagnosability of 5-HT.- E. Histochemical data obtained by destructive extra-situm methods.- IV. The enterochromaffin cell syste.- A. Enterochromaffin cells.- 1. The typical enterochromaffin cell.- a) Specific granules.- ?) Histochemical characteristics.- ?) Histophysical characteristics.- ?) Ultrastructural data.- ?) Data obtained by homogenization and differential centrifugation.- b) Topographical distribution.- ?) Intestinal distribution.- ?) Extra-intestinal localization.- c) Taxonomical distribution.- 2. Brief notes on the argentophil pre-enterochromaffin cells.- 3. Embryology of the enterochromaffin cell.- a) Time of appearance of the enterochromaffin cell.- b) Experimental embryological data.- c) Origin of the enterochromaffin cell.- 4. Various functional conditions of the enterochromaffin cell.- B. Chromaffin cells of the posterior salivary glands of Octopoda.- C. Chromaffin cells in the hypobranchial gland of Muricidae.- D. Cutaneous poison glands in Amphibians.- E. Chromaffin cells in Calliactis parasitica.- F. Poison gland cells of some scorpions.- G. Mast cells in the rat and the mouse.- V. Localizations of phenolic and indolic substances which cannot be referred to 5-H.- VI. Localizations of 5-HT which cannotbe histochemically demonstrated.- VII. Final considerations.- VIII. Technical appendix.- A. Fixations.- 1. Formalin fixation.- 2. Freezing drying.- 3. Fixation for electron-microscopy.- B. Principal reactions.- 1. Chromaffin reactions.- a) Fixation for chromaffin reaction.- b) Reaction on sections.- 2. Iodaffin reactions.- 3. Silver reactions.- a) Argentaffin reaction according to Masson-Hamperl.- b) Argentaffin reaction according to Masson.- c) Methenamine silver argentaffin reaction according to Gomori-Burtner.- d) Bodian’s argyrophil technique.- e) Gross-Schultze’s modification of Bielchowski’s argyrophil technique.- f) Feyrter’s adaptation of Gross-Schultze’s argyrophil technique to paraffin embedded sections.- 4. Schmorl’s reaction.- 5. Diazoreactions.- a) Diazoreaction with the diazotate of sulfanilic acid.- ?) In alkaline solution.- ?) In acid solution.- ?) In alkaline solution with subsequent strong acidification.- b) Diazoreaction with stabilized diazotates.- c) Coupled tetrazonium reaction according to Pearse.- d) Diazosafranin method according to Lillie, Burtner and Henson.- 6. Gibbs’s dichloroquinonechlorimide reaction.- 7. Pearse’s thioindoxyl reaction.- C. Estimation of the weighted index of granularity in the rat according to Ghiringhelli and Mira.- References.- 2: Chemical analysis of indolealkylamines and related compounds.- A. Isolation and fractionation from biological materia.- I. Extraction procedures.- 1. Acetone extraction.- 2. Butanol extraction.- 3. Other solvent extractions.- II. Chromatographic procedures.- 1. Adsorption chromatography.- 2. Ion exchange chromatography.- 3. Paper chromatography.- 4. Molecular sieving (gel filtration).- III. Paper electrophoresis.- B. Identification.- I. Ultraviolet absorbancy.- II.Fluorescence.- III. Colour reactions.- 1. Aldehyde reactions.- 2. Xanthydrol reaction.- 3. l-Nitroso-2-naphthol reaction.- 4. Diazo reactions.- IV. Countercurrent distribution.- V. Paper chromatography.- 1. Chromatography paper.- 2. Solvent systems.- 3. Location of spots.- 4. Rf values of indolealkylamines and related compounds.- 5. Quantitative paper chromatography.- VI. Thin layer chromatography.- VII. Gas chromatography.- VIII. Paper electrophoresis.- C. Quantitative determination of specific compounds.- I. Simple indoles.- 1. Tryptamine.- 2. Tryptophan.- 3. Indoleacetic acid.- II. 5-Hydroxyindoles.- 1. 5-Hydroxytryptamine.- 2. 5-Hydroxytryptophan.- 3. 5-Hydroxyindoleacetic acid.- References.- 3: Bioassay of indolealkylamines.- I. Extraction of 5-HT and related indolealkylamines from tissues and organic fluids.- II. Smooth muscle preparations used in the bioassay of indolealkylamines.- 1. Rat uterus.- a) Erspamer’s original method.- b) Gaddum’s technique.- 2. Rat fundus strip.- 3. Rat colon.- 4. Guinea-pig ileum.- 5. Isolated rabbit ear.- 6. Molluscan heart.- a) Venus inercenaria.- b) Helix (several species).- c) Spisula (Mactra) solida.- d) Anodonta cygnea.- e) Other molluscs.- 7. Miscellaneous preparations.- III. The relative potency of natural and synthetic indolealkylamines.- References.- 4: Occurrence of indolealkylamines in nature.- I. Introduction.- II. Vertebrates.- 1. Gastro-intestinal tract.- 2. Blood.- 3. Spleen.- 4. Mast cells.- 5. Other extracerebral tissues of mammals.- 6. Central and peripheral nervous system.- 7. Venom of reptiles.- 8. Amphibian skin.- 9. Fish tissues and venoms.- 10. Urine.- 11. Biological fluids and liquids other than urine.- III. Invertebrates.- IV. Plants.- References.- 5: Biosynthesis of indolealkylamines. Physiologicalrelease and transport of 5-hydroxytryptamine.- I. Introduction.- II. The hydroxylation of tryptophan.- III. The decarboxylation of 5-hydroxytryptophan.- 1. The identity of 5-hydroxytryptophan decarboxylase with dopa decarboxylease.- 2. Distribution of 5-hydroxytryptophan decarboxylase (dopa decarboxylase) within the body.- 3. Intracellular distribution of 5-hydroxytryptophan decarboxylase (dopa decarboxylase).- 4. Pyridoxal phosphate as a coenzyme of 5-hydroxytryptophan decarboxylase (dopa decarboxylase).- 5. Substrate specificity of 5-hydroxytryptophan decarboxylase (dopa decarboxylase).- 6. Inhibitors of 5-hydroxytryptophan decarboxylase (dopa decarboxylase).- 7. Studies on 5-hydroxytryptophan decarboxylase (dopa decarboxylase) in vivo.- 8. Mechanism of the decarboxylase reaction.- 9. Differences in 5-hydroxytryptophan decarboxylase activity with age.- IV. Biosynthesis of melatonin.- V. Storage of 5-hydroxytryptamine.- VI. Turnover of 5-hydroxytryptamine.- References.- 6: Metabolism of indolealkylamines.- A. Introduction.- B. Enzymes acting on indolealkylamines.- I. Amine oxidases.- 1. The intracellular (and carbonyl-reagent-intensitive) amine oxidase.- a) Preparation of amine oxidase.- b) Intracellular localization of amine oxidase.- c) Distribution of amine oxidase.- d) Histochemistry of amine oxidase.- e) Indolealkylamines as substrates of amine oxidase.- ?) Tryptamine and 5-hydroxytryptamine.- ?) N-substituded amines.- ?) Other indolealkylamines.- 2. Amine oxidases inhibited by carbonyl reagents.- 3. Microsomal deaminating enzymes.- 4. Microsomal demethylating enzymes.- II. Reactions of the phenolic hydroxyl groups.- 1. Hydroxyindole oxidases.- 2. Conjugases and dephosphorylase.- 3. Hydroxyindole-O-methyl transferase.- III. Introduction of the phenolichydroxyl groups.- IV. Introduction of N-methyl groups.- V. N-acetylase.- VI. Oxidative deamination and transamination involving 5-hydroxytryptophan.- 1. Amino-acid oxidases.- 2. Transaminases.- C. Metabolism of indolealkylamines.- I. Metabolites arising from deamination reactions.- 1. Metabolites of tryptamine and of its N-methylated derivatives.- 2. Metabolites of 5-hydroxytryptamine and related amines.- a) 5-Hydroxytryptamine.- b) Other 5-hydroxyindolealkylamines.- c) Derivatives of 5-hydroxyindoles.- 3. 4-Hydroxyindoles.- II. N-Acetylated metabolites.- III. Excretion of O-sulphates.- IV. Excretion of O-glucuronides.- V. Formation and excretion of phenolic compounds.- VI. Metabolism of melatonin.- D. Summary.- References.- 7: Peripheral physiological and pharmacological actions of indolealkylamines. By.- I. Acute toxicity of indolealkylamines.- II. Action on the systemic blood pressure.- III. Action on special vascular areas.- 1. Coronary vascular bed.- 2. Pulmonary vessels.- 3. Liver vessels.- 4. Spleen vessels.- 5. Vessels of the placenta.- 6. Musculo-cutaneous vessels.- 7. Vessels of the kidney.- 8. Brain vessels.- 9. Vessels of the retina.- 10. Vasa vasorum.- 11. Other vascular areas.- 12. Effect of local application of 5-HT.- 13. Action of 5-HT on isolated artery strips or rings.- 14. Conclusive remarks.- IV. Action on vascular permeability.- V. Action on capillary resistance.- a) Action of endogenous 5-HT on capillary resistance.- b) Action of exogenous 5-HT on capillary resistance.- c) Therapeutical trial of 5-HT in haemorrhagic syndromes ascribed to increased capillary fragility.- VI. Participation in the mechanism of haemostasis.- VII. Action on the heart.- 1. Heart in situ.- 2. Heart-lung preparation.- 3. Isolated heart.- 4. Isolated atrium.- 5. Papillary muscle.- 6. Strips of turtle and frog ventricle.- 7. Heart of molluscs.- 8. Heart of crustaceans.- VIII. Action on the circulation and the function of the kidney.- IX. Action on cellular permeability.- X. Action on extravascular smooth muscles.- 1. Gastro-intestinal tract.- 2. Extrahepatic biliary tract.- 3. Bronchial smooth muscle.- 4. Uterus.- 5. Urinary bladder.- 6. Ureter.- 7. Seminal vesicles.- 8. Spleen.- 9. Nictitating membrane.- 10. Iris smooth muscle.- 11. Chick amnion.- 12. Molluscan smooth muscle.- 13. Muscles of worms.- 14. Muscles of sea anemones.- XI. Action on respiration.- XII. Action on external secretions.- 1. Salivary secretion.- 2. Gastric secretion.- 3. Pancreatic and biliary secretions.- 4. Sweat secretion.- XIII. Metabolic effects. Action on enzymes.- 1. Action on carbohydrate metabolism.- 2. Action on oxygen consumption.- 3. Action on fat content in peripheral blood.- 4. Action on intestinal absorption of calcium and water.- 5. Miscellaneous metabolic effects.- 6. Inhibition of lipide peroxide formation in tissues.- 7. Action on cholinesterases.- 8. Action on ceruloplasmin.- 9. Action on phenol oxidases.- 10. Miscellaneous effects on enzymes.- XIV. Action on chromatophores.- 1. 5-Hydroxytryptamine.- 2. Melatonin.- XV. Action on endocrine glands. Inter-endocrine correlations.- 1. Anterior hypophysis.- 2. Supraoptico-hypophyseal tract.- 3. Adrenals.- 4. Thyroid.- 5. Pineal gland.- 6. Testes.- 7. Ovary.- 8. Pancreas.- XVI. Protective action of indolealkylamines in experimental tissue injury.- 1. Radiation injury.- a) Reduction of radiation lethality.- b) Effects of 5-HT on response of tumours to in vivo irradiation.- c) Radioprotective action of 5-HT in vegetables.- d) Effect of 5-HT on irradiation-induced mutation rate of bacteria.- e) Mechanism ofthe radioprotective action of 5-HT.- 2. Liver cirrhosis.- 3. Cardiac and renal necroses.- XVII. Miscellaneous effects.- 1. Action on striated muscle.- 2. Action on the gill cilia of molluscs.- 3. Action on lymph flow.- 4. Action on intra-ocular pressure.- 5. Histamine-releasing activity.- 6. Action on phagocytosis.- 7. Action on tumour growth.- 8. Action on pigment formation.- 9. Action on bioluminescence.- 10. Action on growth of plant tissues.- 11. Action on food intake.- 12. Action on metamorphosis in amphibians.- 13. Inhibition of mitochondria swelling.- 14. Action on brain microsomes.- 15. Action on cerebro-spinal fluid pressure.- 16. Action on collagen.- 17. Teratogenic effect References of Chapter 7 see at the end of Chapter 8..- 8: Participation of 5-hydroxytryptamine in physiopathological processes.- I. Anaphylaxis.- 1. Mouse.- 2. Rat.- 3. Guinea-pig.- 4. Rabbit.- 5. Dog.- 6. Man.- 7. Chicken.- II. Anaphylactoid reaction.- 1. Egg-white, ovomucoid, dextran, polyvinylpyrrolidone, compoud 48/80.- 2. Formalin.- III. Other immunological reactions.- 1. Rabbit.- 2. Guinea-pig.- 3. Rat.- 4. Mouse.- IV. Response to bacterial toxins.- V. Inflammatory processes.- 1. Bacterial inflammation.- 2. Turpentine inflammation.- 3. Thermal injury.- 4. Ultraviolet irradiation.- 5. X-ray irradiation.- 6. Response to snake venoms.- VI. Formation of granulation tissue and healing of wounds.- VII. Reaction to stress.- VIII. Miscellaneous experimental pathological processes.- 1. Haemorrhagic shock.- 2. Transfusional reaction.- 3. Complications in extracorporeal circulation.- 4. Pulmonary thromboembolism.- 5. Ozone-induced pulmonary oedema.- 6. Decompression sickness.- 7. Reaction to air ions and microparticle inhalation.- 8. Dumping-syndrome.- 9. Calciphylactic muscular distrophy.- 10. Osteolathyrism.- 11. Reactive hyperaemia.- 12. Poisoning produced by putrefied fish.- References.- 9: Pharmacological actions of indolealkylamines and precursor aminoacids on the central nervous system.- A. Effects on behaviour.- I. 5-Hydroxytryptamine.- 1. Mouse.- 2. Rat.- 3. Rabbit.- 4. Cat.- 5. Dog.- 6. Pigeon.- 7. Fish.- 8. Frog.- II. 5-Hydroxytryptophan.- 1. Mouse and rat.- 2. Rabbit.- 3. Cat.- 4. Dog.- 5. Pigeon.- III. Bufotenine.- 1. Rat.- 2. Dog.- 3. Monkey.- IV. Psilocybin.- 1. Mouse.- 2. Rabbit.- 3. Monkey.- 4. Spider.- V. Tryptamine and tryptophan.- VI. Other indolealkylamines.- B. Passage of 5-HT through the blood-brain barrier.- C. Effects on the body temperature.- D. Interferences with central acting drugs.- I. Hypnotics and anaesthetics.- 1. 5-Hydroxytryptamine.- 2. 5-Hydroxytryptophan.- 3. Bufotenine and psilocybin.- 4. Tryptamine and tryptophan.- II. Convulsants.- III. Other central acting drugs.- E. Drugs and treatments affecting the brain 5-HT content.- I. Electroshock and convulsants.- II. Anticonvulsant drugs.- III. Barbiturates and other central depressant drugs.- IV. Cortisone.- V. Central nervous system lesions.- F. Effects on the electroencephalogram.- I. 5-Hydroxytryptamine.- 1. Rabbit.- 2. Cat.- II. 5-Hydroxytryptophan.- 1. Rabbit.- 2. Cat.- III. Other indolealkylamines and precursor aminoacids.- G. Effects on action potentials evoked in cerebral cortex and in subcortical structures.- I. 5-Hydroxytryptamine.- 1. Responses of the cerebral cortex to direct electrical or chemical stimulation.- 2. Cortical and subcortical responses evoked by afferent impulses.- a) Transcallosal stimulation.- b) Sensory nerves and sense organs stimulation.- II. 5-Hydroxytryptophan.- III. Other indolealkylamines.- H. Effects on spinal reflexes.- I. 5-Hydroxytryptamine.- II. Psilocybin and psilocin.- III. Bufotenine.- IV. Other indolealkylamines.- I. Effects on single cellular elements.- I. Single neurones.- II. Brain cells cultured “in vitro”.- J. Effects on sympathetic ganglia.- I. 5-Hydroxytryptamine.- II. Other indolealkylamines.- K. Effects on cutaneous sensory endings.- L. Effects on the central nervous system of lower animals.- References.- 10: Drugs which antagonize 5-hydroxytryptamine and related indolealkylamines.- A. Introduction.- B. Reviews of antagonists of 5-HT.- C. General description of 5-HT antagonists.- 1. Relations of 5-HT and its antagonists to the “specific” tissue receptors.- 2. Relations of 5-HT and its antagonists to other biological sites reacting with 5-HT..- 3. Relations of indolealkylamines other than 5-HT to the 5-HT receptors.- D. Methods.- 1. Critical considerations of methods for assessing blocking action to 5-HT and related indolealkylamines.- 2. Methods for testing anti-5-HT action (Tables).- E. Classes of anti-5-HT drugs (Tables).- F. Neurotropic antagonists of 5-HT.- G. Actions of antagonists of 5-HT on the CNS.- 1. Summary of the actions of antagonists on the CNS effects produced by 5-HT.- 2. Influence of antagonists on CNS effects produced by 5-HT precursors and releasing agents.- H. Effects on the CNS of indolealkylamines related to 5-HT.- I. Action of 5-HT antagonists in inflammatory and anaphylactic processes.- K. Clinical applications of antagonists of 5-HT.- L. Biological data of the available antagonists of 5-HT (Tables).- M. Conclusions.- References.- 11: Drugs which block the storage of 5-hydroxytryptamine and related amines..- I. Introduction.- II. Reserpine.- A. Chemistry and metabolism.- B. Effects on monoamine levels in tissues.- a) Effects of a single dose or short-termtreatment.- b) Effects of long-term treatment.- C. Effects on monoamines in body fluids and on their metabolites in body fluids and tissues.- D. Effects on uptake of monoamines.- a) In-vitro experiments.- b) In-vivo experiments.- E. Miscellaneous biochemical actions.- a) Adenosine phosphates.- b) Carbohydrates etc.- c) ?-Aminobutyric acid.- d) Histamine.- e) Acetylcholine.- f) Lipids.- F. Survey of pharmacology of reserpine.- a) Effects on behaviour and various brain functions.- b) Effects on the autonomic nervous system.- c) Endocrine effects.- d) Cumulation and tolerance.- G. Interaction between reserpine and other drugs and factors.- a) Tetrabenazine.- b) Monoamine oxidase inhibitors.- c) Monoamine analogs and precursors.- d) Other agents.- e) Exposure to high and low temperatures.- f) Diet.- g) Functional activity and rate of turnover.- III. Other Rauwolfia alkaloids.- IV. Tetrabenazine and other benzoquinolizines.- A. Chemistry and metabolism.- B. Effects on monoamine metabolism.- C. Pharmacology.- V. Other agents.- VI. Concluding remarks on the functional significance of the effect of reserpine-like drugs on tissue monoamines.- References.- 12: Inhibitors of monoamine oxidase and decarboxylase of aromatic amino acids..- I. Introduction.- II. Monoamine oxidase.- A. Biochemistry of the enzyme.- 1. Reaction formula.- 2. Differentiation.- 3. Substrates.- 4. Tissue distribution.- 5. Purification and properties.- 6. Active center and reaction mechanism.- 7. Determination.- a) Disappearance of substrate.- b) Reduction of electrone acceptors.- c) Oxygen consumption.- d) Ammonia formation.- e) Peroxyde formation.- f) Formation of aldehyde.- g) Accumulation of a carboxylic acid.- h) Formation of dark pigments.- 8. Physiological role.- B. Monoamine oxidase inhibitors.- 1.Chemical classification.- a) Hydrazine derivatives.- ?) Monoalkyl-, monoaryl-, and monoaralkyl-hydrazines.- ?) Di-alkyl-,diaralkyl-, and alkyl-aralkylhydrazines.- ?) Hydrazones.- ?) N-Acylated alkyl- and aralkylhydrazines.- ?) Cyclichydrazines.- b) 2-Phenylcyclopropylamine and derivatives.- c) N-Benzyl-N-methyl-propargylamine and derivates.- d) 2-Methyl-3-piperidinopyrazine.- 2. Distribution and metabolism in tissues.- a) Hydrazines.- ?) Distribution and excretion.- ?) Metabolism.- b) Other compounds.- 3. Effect on monoamine oxidase.- a) Hydrazine derivatives.- b) Phenylcyclopropylamine.- c) N-Benzyl-N-methyl-propargylamine and derivatives.- d) 2-Methyl-3-piperidinopyrazine.- 4. Effects on other enzyme systems.- a) Other amine oxidases.- ?) Amphetamine oxidase.- ?) Diamine oxidases.- ?) D- and ophio-amino acid oxidase.- b) Other oxidases.- ?) Ceruloplasmin.- ?) Choline oxidase.- ?) Succinate dehydrogenase.- ?) Dopamine-?-oxidase.- ?) Various oxi-doreductases.- ?) Peroxidases.- c) Hydrolases.- d) Enzymes related to pyridoxal-5?-phosphate.- e) Other enzymes.- f) Respiration and glycolysis.- 5. Effects on metabolism.- a) Monoamines.- ?) Endogenous monoamines.- ?) Exogenous monoamines and monoamine precursors.- ?) Counteraction against monoaminereleasers.- ?) Interaction of short- and long-acting MAO inhibitors.- ?) Mechanism of action.- b) Other metabolic effects.- ?) Carbohydrate metabolism and oxygen consumption.- ?) Di-amines and other amines.- ?) Vitamin B6.- ?) Varia.- 6. Pharmacodynamic effects.- a) Effects mainly connected with monoamine oxidase inhibition.- ?) Modification of the action of exogenous monoamines and their precursors.- ?) Counteraction of monoamine releasers.- ?) Anticonvulsant effect.- ?) Synaptic and neuraltransmission.- b) Effects of doubtful connection with monoamine oxidase inhibition.- ?) Behaviour.- ?) Electroencephalogram (EEG).- ?) Cardiovascular effects.- ?) Gastrointestinal tract.- ?) Influence on the action of various drugs.- ?) Other effects.- ?) Toxicity.- General toxicity.- Organ toxicity.- Other effects.- 7. On the mode of action of monoamine oxidase inhibitors in human disease.- a) Antidepressive effect.- b) Hypotensive effect.- c) Antistenocardic effect.- C. Summary.- III. Decarboxylases of aromatic amino acids.- A. Biochemistry of the enzyme.- 1. Reaction formula.- 2. Differentiation.- 3. Substrates.- 4. Tissue distribution.- 5. Purification and properties.- Coenzyme.- 6. Determination.- 7. Physiological role.- B. Inhibitors of decarboxylase of aromatic l-amino acids.- 1. ?-Alkylated aromatic amino acids.- a) Chemistry and action on the enzyme.- b) Effect on other enzymes.- c) Tissue distribution and metabolism.- d) Effects on metabolism.- ?) Endogenous monoamines.- ?) Exogenous aromatic aminoacids.- ?) Exogenous monoamines.- ?) Other metabolic effects.- e) Pharmacodynamic effects.- ?) Cardiovascular effects.- ?) Effects on the central nervous System.- ?) Interference with exogenous monoamines, monoamine precursors, and drugs.- ?) Other effects.- 2. Hydrazine derivatives and oxygen isosters.- a) Chemistry and action on the enzyme.- b) Effects on other enzymes.- c) Tissue distribution and metabolism.- d) Effects on metabolism.- ?) Endogenous monoamines.- ?) Exogenous aromatic amino acids.- e) Pharmacodynamic effects.- 3. Derivatives of hydroxycinnamic acid.- a) Chemistry and action on the enzyme.- b) Tissue distribution and metabolism.- c) Effect on monoamine metabolism.- d) Pharmacodynamic effects.- C. Summary.- IV. Concluding remarks.-Acknowledgements.- References.- 13: 31orphological changes caused by injections of 5-HT in animals and man.- Blood.- Cardiovascular system.- Gastrointestinal tract.- Kidney.- Liver.- Reproductive system.- Other tissues.- References.- 14: Clinical aspects of cerebral and extracerebral 5-hydroxytryptamine.- A. The distribution of 5-hydroxytryptamine in man.- a) Blood.- b) Central nervous system.- c) Alimentary canal.- d) Urine.- B. Effects following infusions of 5-hydroxytryptamine.- a) Subjective symptoms.- b) Cardiovascular system.- c) Respiration.- d) Renal function.- e) Gastrointestinal tract.- f) Effect of an infusion of 5-HT on the concentration of 5-HT in the blood.- g) The metabolism and excretion of infused 5-HT.- h) The metabolism and excretion of 5-HT ingested orally.- i) Intradermal injections of 5-HT.- C. Effects following an infusion of 5-hydroxytryptophan (5-HTP).- D. Effect of diet and drugs on hydroxindoles in blood and urine.- a) Diet.- b) Purgatives and carbachol.- c) Other drugs.- E. 5-Hydroxytryptamine in disease.- 1. Carcinoid disease.- 2. The malignant carcinoid syndrome.- a) The flush.- b) Intestinal symptoms.- c) Bronchoconstriction.- d) Cardiac lesions.- e) Other symptoms and signs.- 3. The carcinoid tumour.- Chemical and biochemical observations.- 4. The blood of patients with carcinoid tumours.- a) 5-Hydroxytryptamine.- b) Other hydroxyindoles.- c) Histamine.- 5. The urine of patients with the carcinoid syndrome.- 5-Hydroxyindoles.- 6. Causation of symptoms.- a) The flush.- b) Gastrointestinal and respiratory symptoms.- c) Cardiovascular lesions.- d) Other symptoms.- 7. Treatment of the malignant carcinoid syndrome.- a) Surgical treatment.- b) Drug therapy.- 8. Hyperserotonaemia without increased 5-HIAA excretion.- 9. Other diseases of the alimentary canal.- 10. Diseases of the blood and blood forming organs.- 11. Diseases of the cardiovascular system.- 12. Mental deficiency.- 13. Other diseases of the central nervous system.- a) Schizophrenia.- b) Parkinsonism.- 14. Miscellaneus conditions.- Menstruation, Pregnancy, Menopausal flushing.- 15. Clinical use of 5-hydroxytryptamine antagonists.- 16. 5-Hydroxytryptamine and anaphylaxis in man.- 17. Administration of other indolealkylamines to man.- References.- Author Index.