5-Hydroxytryptamine and Related Indolealkylamines

Inhaltsverzeichnis

• 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.
• 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.
• 4: Occurrence of indolealkylamines in nature.
• 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.
• 5: Biosynthesis of indolealkylamines. Physiologicalrelease and transport of 5-hydroxytryptamine.
• 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.
• 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.
• 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.
• 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.
• 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.
• 9: Pharmacological actions of indolealkylamines and precursor aminoacids on the central nervous system.
• A. Effects on behaviour.
• I. 5-Hydroxytryptamine.
• 3. Rabbit.
• 4. Cat.
• 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.
• 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.
• 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.
• 2. Cat.
• III. Other indolealkylamines and precursor aminoacids.
• G. Effects on action potentials evoked in cerebral cortex and in subcortical structures.
• 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.
• III. Other indolealkylamines.
• H. Effects on spinal reflexes.
• II. Psilocybin and psilocin.
• IV. Other indolealkylamines.
• I. Effects on single cellular elements.
• I. Single neurones.
• II. Brain cells cultured “in vitro”.
• J. Effects on sympathetic ganglia.
• II. Other indolealkylamines.
• K. Effects on cutaneous sensory endings.
• L. Effects on the central nervous system of lower animals.
• 10: Drugs which antagonize 5-hydroxytryptamine and related indolealkylamines.
• 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.
• 11: Drugs which block the storage of 5-hydroxytryptamine and related amines..
• 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.
• 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.
• 12: Inhibitors of monoamine oxidase and decarboxylase of aromatic amino acids..
• 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.
• b) Phenylcyclopropylamine.
• c) N-Benzyl-N-methyl-propargylamine and derivatives.
• 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.
• 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.
• ?) Exogenous aromatic aminoacids.
• ?) Exogenous monoamines.
• ?) Other metabolic effects.
• e) Pharmacodynamic effects.
• ?) Effects on the central nervous System.
• ?) Interference with exogenous monoamines, monoamine precursors, and drugs.
• 2. Hydrazine derivatives and oxygen isosters.
• b) Effects on other enzymes.
• ?) Exogenous aromatic amino acids.
• 3. Derivatives of hydroxycinnamic acid.
• b) Tissue distribution and metabolism.
• c) Effect on monoamine metabolism.
• d) Pharmacodynamic effects.
• IV. Concluding remarks.
• Acknowledgements.
• 13: 31orphological changes caused by injections of 5-HT in animals and man.
• Blood.
• Cardiovascular system.
• Gastrointestinal tract.
• Kidney.
• Liver.
• Reproductive system.
• Other tissues.
• 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.
• b) Other hydroxyindoles.
• c) Histamine.
• 5. The urine of patients with the carcinoid syndrome.
• 5-Hydroxyindoles.
• 6. Causation of symptoms.
• 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.
• Author Index.