5-Hydroxytryptamine and Related Indolealkylamines
5-Hydroxytryptamine and Related Indolealkylamines
The study of biogenic amines, which from the beginning of modern pharma cology has always attracted the enthusiastic attention of research workers and has led to some of the most brilliant and illuminating experimental results in biology, has been unexpectedly extended in the last fifteen years. 'With the discovery of 5. hydroxytryptamine (enteramine, serotonin), in fact, the vast field of indole alkylamines has been opened up for research. In a decade of intensive and dedicated work, an immense amount of experi mental data has been collected, the significance of which, having rapidly overrun the limits of pharmacology, physiology, and biochemistry, has spread into all fields of biology and medicine, as previously occurred with choline esters, catechol amines and imidazolealkylamines. Thus, the study of indolealkylamines, espe cially that of their metabolism, has led not only to explanation of the mechanism of action, formerly largely obscure, of some important drugs, to clarification of the pathogenesis of some morbid syndromes and to a parallel flourishing of research on other biogenic amines, but also to surprising achievements in the field of therapeutics. The discovery of monoamineoxidase and dopadecarboxylase inhibitors, and of drugs which block the storage of biogenic amines in the body depots are among the most striking results of research on the indolealkylamines.
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.
1. Histology of the enteroehromaffin cell system
I. IntroductionII. 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.
Erspamer, Vittorio
ISBN | 978-3-642-85469-9 |
---|---|
Artikelnummer | 9783642854699 |
Medientyp | Buch |
Auflage | Softcover reprint of the original 1st ed. 1966 |
Copyrightjahr | 2012 |
Verlag | Springer, Berlin |
Umfang | XX, 928 Seiten |
Abbildungen | XX, 928 p. |
Sprache | Englisch |