Psychotropic Agents: Part II: Anxiolytics, Gerontopsychopharmacological Agents, and Psychomotor Stimulants by C. BraestrupPsychotropic Agents: Part II: Anxiolytics, Gerontopsychopharmacological Agents, and Psychomotor Stimulants by C. Braestrup

Psychotropic Agents: Part II: Anxiolytics, Gerontopsychopharmacological Agents, and Psychomotor…

byC. Braestrup

Paperback | November 15, 2011

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This second volume continues the description of the psychotropic agents and discusses anxiolytics, gerontopsychopharmacological agents, and psychomotor stimulants. Of these groups of substances, most of this volume has been devoted to anxiolytics as the authors have endeavored to convey as complete a picture as possible. The editors are of the opinion that particular attention should be given to anxiolytics with regard to their range of administration as this is the most frequently prescribed group of psychotropic drugs. In contrast to neuroleptics and thymoleptics, anxiolytics are a class of psychotropic drugs whose therapeutic effect can be recognized in animal experiments to some extent. This, together with the analysis of the biochemical mechanisms of their actions, permits a better understanding of material processes in the brain accompanying the emotions: anxiety and tension. For the first time in the history of the Handbook the editors have devoted a whole chapter to gerontopsychopharmacological agents. In doing so they are also aware of the risk they are taking, at least from a pharmacological point of view, as gerontopsychopharmacological agents are an insufficiently defined and extremely heterogeneous group of substances. The only denominator the various subgroups of these agents have in common is that they are given in cases of dysfunctions, disorders, and diseases of the brain occurring mainly in the elderly.
Title:Psychotropic Agents: Part II: Anxiolytics, Gerontopsychopharmacological Agents, and Psychomotor…Format:PaperbackDimensions:780 pages, 24.4 × 17 × 0.07 inPublished:November 15, 2011Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

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ISBN - 10:364267769X

ISBN - 13:9783642677694

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Table of Contents

Anxiolytics.- 1 The Chemistry of Anxiolytics.- A. Introduction.- B. Classes of Antianxiety Agents.- I. Barbiturates.- II. Propanediols.- III. Compounds Belonging to Various Chemically Unrelated Classes.- IV. 1,4-Benzodiazepines.- V. 1,5-Benzodiazepines.- References.- 2 General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives.- A. Acute Toxicity.- I. Acute Toxicity in Man.- II. Acute Toxicity in Animals.- III. General Comments on Acute Toxicity.- B. Cardiovascular Effects.- I. Blood Pressure, Heart Rate, and Other Hemodynamic Parameters.- II. Arrhythmias.- III. Isolated Myocardium.- IV. Cardiovascular Responses to Central Nervous System Stimulation.- V. Cardiovascular Responses to Behavioral Experiments.- VI. Cardiovascular Responses to Peripheral Stimulation.- VII. Cardiac and Vasoconstrictor Responses to Various Agents..- VIII. Conclusions.- C. Effects on Respiration.- I. Respiratory Control.- II. Cough.- III. Bronchospasm.- IV. Conclusions.- D. Effects on the Gastrointestinal System.- I. Stomach.- II. Liver and Pancreas.- III. Gastrointestinal Motility.- IV. Conclusions.- E. Effects on Other Autonomic Funtions.- F. Effects on Motor End Plate and Skeletal Muscle.- I. Neuromuscular Transmission In Vivo.- II. In Vitro Neuromuscular Preparations.- III. Effects on Invertebrate Musculature.- IV. Effects on Embryonic Muscles.- V. Interaction with Neuromuscular Blockers.- VI. Conclusions.- G. Effects on the Kidney and Body Fluid Electrolytes.- I. Urine.- II. Blood Electrolytes.- III. Sodium Current in Frog Skin.- IV. Calcium Content of Synaptic Vesicles.- H. Effects on the Endocrine System.- I. Male and Female Sexual Hormones.- II. Thyroid Hormones.- III. Pituitary Hormones.- IV. Conclusions.- I. Effects on Cell Metabolism.- I. Carbohydrates.- II. Energy-Rich Phosphates.- III. Lipids.- IV. Protein Synthesis.- V. Miscellaneous.- VI. Conclusions.- J. Miscellaneous Effects.- I. Nociception.- II. Inflammation.- III. Food and Fluid Intake.- IV. Emesis.- V. Body Temperature.- VI. Conclusions.- K. Anticonvulsant Activity.- I. Acute Models of Epilepsy.- II. Chronic Models of Epilepsy.- III. Conclusions.- L. Effects on Muscle Tone and Coordination.- I. Subjective Methods of Evaluating Muscle Tone and Coordination.- II. Objective Tests Believed to Record Muscle Tone.- III. Conclusions.- M. Effects on Spontaneous and Induced Motor Activity.- I. Locomotor Activity.- II. Exploratory Behavior.- III. Effects on Drug-Induced Changes in Motor Activity.- IV. Induced Head-Turning.- V. Conclusions.- N. Benzodiazepines and Aggression.- I. Spontaneous Aggression.- II. Isolation-Induced Aggression in Mice.- III. Aggression in Grouped Male Mice.- IV. Foot-Shock-Induced Aggression in Mice.- V. Aggression Induced in Rats by Brain Lesions.- VI. Brain Stimulation-Induced Aggression in Cats, Rats, and Monkeys.- VII. Drug-Induced Aggression.- VIII. Induction of Aggressive Behavior.- IX. Conclusions.- O. Interaction with Other Centrally Active Agents.- I. Synergism with "Centrally Depressant" Agents.- II. Antagonism with Centrally Active Agents.- III. Conclusions.- P. Effects on Peripheral Nervous Structures.- I. Axonal Conduction.- II. Spontaneous and Evoked Activity in Sympathetic and Parasympathetic Nerves.- III. Synaptic Transmission in Sympathetic Ganglia.- IV. Dorsal Root Ganglia.- V. Conclusions.- Q. Effects on Invertebrate Neurons.- R. Effects of Spinal Cord Functions.- I. Effects on Spinal Cord Activities Through a Supraspinal Site of Action.- II. Effects Within the Spinal Cord.- III. Conclusions.- S. Effects on Dorsal Column Nuclei.- T. Benzodiazepines and Evoked Potentials in the Brain.- I. Limbic Structures.- II. Hypothalamus and Thalamus.- III. Substantia Nigra.- IV. Brain Stem Reticular Formation.- V. Lateral Vestibular Nucleus.- VI. Visual System.- VII. Cerebral Cortex.- VIII. Conclusions.- U. Effects on Cortical and Subcortical Electroencephalogram (EEG).- I. Spontaneous EEG.- II. Arousal Reaction.- III. Hippocampal Theta-Rhythm.- IV. Cortical Recruiting and Augmenting Response.- V. Caudate Spindles.- VI. Ponto-geniculo-occipital (PGO) Waves.- VIL Afterdischarges.- VIII. Conclusions.- V. Benzodiazepines and Sleep.- I. Cats.- II. Rabbits.- III. Rats.- IV. Monkeys.- V. Ponto-geniculo-occipital (PGO) Waves.- VI. Conclusions.- W. Effects on Single- and Multiple-Unit Activity in the Brain.- I. Limbic System.- II. Cerebellum.- III. Cerebral Cortex.- IV. Brain Stem and Diencephalic Structures.- V. Conclusions.- X. Effects on Specific Neurotransmitter and Mediator Systems.- I. Acetylcholine (ACh).- II. Dopamine (DA).- III. Noradrenaline (NA).- IV. Adrenaline.- V. Phenylethylamine.- VI. 5-Hydroxytryptamine (5-HT).- VII. Histamine.- VIII. Glutamate.- IX. Glycine.- X. ?-Aminobutyric Acid (GABA).- XI. Purine Nucleotides.- XII. Enkephalins.- XIII. Other Peptides.- XIV. Prostaglandins.- XV. Conclusions.- Y. Benzodiazepines and Cyclic Nucleotides.- I. Cyclic 3?,5?-Adenosine Monophosphate (cAMP).- II. Cyclic 3?,5?-Guanosine Monophosphate (cGMP).- III. Conclusions.- Z. Benzodiazepine Receptors.- I. Main Characteristics of Benzodiazepine Receptors.- II. Regional Distribution of Benzodiazepine Receptors.- III. Multiplicity of Benzodiazepine Receptors.- IV. Influence of Physical Factors on Benzodiazepine Binding.- V. Nature of the Benzodiazepine Binding Site.- VI. Cellular Localization of Benzodiazepine Receptors.- VII. Subcellular Localization.- VIII. Phylogenetic Development of Benzodiazepine Receptors.- IX. Ontogenetic Development of Benzodiazepine Receptors.- X. In Vivo Demonstration of Benzodiazepine Receptors.- XI. Plasticity of Benzodiazepine Receptors.- XII. Endogenous Ligands for Benzodiazepine Receptors.- XIII. Modulation of Benzodiazepine Binding by GABA-Mimetic Compounds.- XIV. Enhancement of 3H-Diazepam Binding by Other Compounds.- XV. Molecular Consequences of Benzodiazepine Receptor Stimulation.- AA. Benzodiazepine Antagonists.- AB. Concluding Remarks.- References.- Addendum.- 3 General Pharmacology and Neuropharmacology of Propanediol Carbamates.- A. Introduction.- B. Acute Toxicity.- C. Cardiovascular Actions.- I. Meprobamate.- II. Mebutamate.- D. Effects on Respiration.- E. Effects on Other Autonomic Functions.- I. Gastrointestinal System.- F. Effects on Neuromuscular Transmission.- G. Effects on the Endocrine System.- H. Anticonvulsant Activity.- I. Effects on Spontaneous and Imposed Motor Activity.- J. Effects on Muscle Tone and Coordination.- K. Interactions with Various Centrally Active Agents.- L. Effects on Aggression.- M. Effects on Spinal Cord Activities.- N. Effects on Evoked Potentials in the CNS.- O. Effects on the EEG.- P. Effects on Sleep.- Q. Effects on Specific Neurotransmitter Systems.- R. Effects on Brain Energy Metabolism.- S. Concluding Remarks.- References.- 4 Behavioral Pharmacology of Anxiolytics.- A. Introduction.- B. History.- C. Behavioral Pharmacology in Humans.- I. Effects on Verbal Behavior.- II. Effects on Somatic-Autonomic Functions.- III. Effects on Productive Activities.- IV. Miscellaneous Effects.- D. Behavioral Pharmacology in Animals.- E. Conclusion.- References.- 5 Biochemical Effects of Anxiolytics.- A. Introduction.- B. Benzodiazepine Receptors.- I. General Properties.- 1. Binding Characteristics.- 2. Distribution.- 3. Brain Specificity.- 4. Ontogenetic and Phylogenetic Development of Benzodiazepine Receptors.- II. Pharmacological Specificity.- III. Neuronal Localization.- IV. In Vivo Receptor Modifications.- V. In Vitro Receptor Modulation.- 1. GABA (?-Amino Butyric Acid).- 2. Miscellanous Modulators.- VI. Endogenous Ligands.- C. Benzodiazepines and GABA.- I. Electrophysiological and Biochemical Interaction.- II. GABA Turnover.- III. Enzymes.- IV. GABA Uptake.- V. Interaction with GABA-Receptors.- VI. Cyclic GMP.- VII. Conclusion.- D. Benzodiazepines and Serotonin.- I. Serotonin Receptors.- II. Serotonin Level and Metabolism.- E. Benzodiazepines and Acetylcholine.- I. Acetylcholine Level.- II. Acetylcholine Receptors.- F. Benzodiazepine and Catecholamines.- I. Catecholamine Turnover.- II. Indirect Effect on Catecholamines.- III. Dopamine Receptors.- IV. Other Minor Tranquillizers.- G. Miscellaneous.- I. Glycine Receptors.- II. Phosphodiesterases.- III. Glucose Metabolism.- IV. Chloride Channels.- References.- 6 Pharmacokinetics and Metabolism of Anxiolytics.- A. Introduction.- B. Benzodiazepines.- I. Biotransformation Pathways.- II. Pharmacokinetic Profiles.- 1. Single Dose Pharmacokinetics.- 2. Distribution Characteristics.- 3. Elimination Rate Characteristics.- 4. Intramuscular Absorption.- 5. Multiple Dose Pharmacokinetics.- III. Influence of Physiologic and Pathologic Variables on Pharmacokinetics.- 1. Age.- 2. Hepatic Disease.- 3. Renal Disease.- C. Pharmacokinetic Profiles of Meprobamate and Propanediol Carbamates.- I. Single Dose Pharmacokinetics.- II. Multipe Dose Studies.- III. Clinical Toxicology.- IV. Structure Correlations.- D. Summary.- References.- 7 Toxicology and Side-Effects of Anxiolytics.- A. Introduction.- I. Ubiquity of Anxiety.- II. Use of Anxiolytic Drugs.- III. Scope of Present Discussion.- IV. Definition of Adverse Reactions.- B. Benzodiazepines.- I. Adverse Psychiatric Reactions.- 1. Tolerance/Dependence.- 2. Overdose.- 3. Disinhibiting Actions.- 4. Depression.- II. Adverse Neurologic Reactions.- III. Adverse Reactions Due to Drug Interactions.- 1. Ethanol.- 2. Phenytoin.- 3. Enzyme Induction.- IV. Adverse Reactions Due to Allergy.- 1. Skin.- 2. Hematology.- 3. Hepatotoxicity.- V. Teratogenic and Cytogenic Studies.- C. Barbiturates.- I. Adverse Psychiatric Reactions.- 1. Tolerance/Dependence.- 2. Overdose.- 3. Disinhibiting Actions.- 4. Depression.- II. Adverse Neurologic Reactions.- III. Adverse Reactions Due to Drug Interactions.- 1. Ethanol.- 2. Other Drug Interactions.- IV. Adverse Reactions Due to Allergy.- 1. Skin.- 2. Hematology.- 3. Hepatotoxicity.- V. Teratogenic Studies.- D. Concluding Remarks.- References.- 8 Dependence-Producing Effects of Anxiolytics.- A. Pharmacodynamic Profiles.- B. Dependence-Producing Properties.- I. Tolerance.- II. Cross Tolerance.- III. Types of Dependence.- 1. Physical.- 2. Cross Physical.- 3. Psychological.- C. Summary.- References.- Gerontopsychopharmacological Agents.- 9 Chemistry of Gerontopsychopharmacological Agents.- A. Introduction.- B. Alkaloids.- I. Dihydroergopeptines.- II. Ergolines.- III. Vincamine Alkaloids.- IV. Isoquinoline Alkaloids.- C. Derivatives of Piperazine.- D. Derivatives of Phenoxyacetic Acid.- E. Derivatives of Phenylethanolamine.- F. Derivatives of Vitamin B 6.- G. Derivatives of Xanthine.- H. Miscellaneous Compounds.- I. Conclusions.- References.- 10 Pharmacologic Approaches to Gerontopsychiatry.- A. Gerontopsychopharmacologic Agents.- B. Gerontopsychiatric Patients.- C. Current Theories of Aging.- I. Exogenous Causes.- II. Endogenous Causes.- D. Animal Models in Gerontopsychopharmacology.- I. Models Derived from Current Theories.- II. Models of Acute Brain Failure.- III. Models Derived from Impairment of Synaptic Transmission.- E. Three Examples of Gerontopsychopharmacologic Agents.- I. Vincamine.- II. Co-Dergocrine Mesylate.- 1. Metabolic Effects.- 2. Synaptic Transmission.- 3. Behavior.- III. Piracetam.- 1. Neurophysiology Effects.- 2. Metabolic Effects.- 3. Behavioral Effects.- F. Concluding Remarks.- References.- 11 Experimental Behavioral Pharmacology of Gerontopsychopharmacological Agents.- A. Introduction.- B. Studies in Old Animals.- I. Life-Span Studies.- II. EEG and Evoked Potentials.- III. Reactivity to Stress.- IV. Learning and Memory.- 1. Thermic Decompensation.- 2. Passive Avoidance.- 3. Appetitive Maze Learning.- 4. Conditioned Avoidance Response (CAR).- 5. Short-Term Memory in Aged Monkeys.- 6. "Threshold" Active Avoidance.- C. Progeria Models.- D. Studies in Young Adults.- I. "Deficient" Animals.- 1. Brain Ischemia.- 2. Hypoxia.- 3. Sociosensory Deprivation.- II. Standard Young Adults.- 1. Preliminary Considerations.- 2. "Amnesic" Procedures.- 3. Memory-Related Psychophysiological Models.- E. Final Remarks.- References.- 12 Cerebrovascular Agents in Gerontopsychopharmacotherapy.- A. Introduction.- B. Some Mechanisms of Vasoactive Pharmacologic Intervention in Cerebrovascular Disorders.- I. Receptor Agonistic and Antagonistic Mechanisms.- II. Direct Effects on Cerebrovascular Smooth Muscle.- III. Mechanisms Involving Blood and Blood Vessel Wall Interactions.- C. The Drugs.- I. Drugs with Vascular Receptor-Agonistic and -Antagonistic Properties.- II. Drugs with Direct Vascular Smooth Muscle Effects.- III. Nonspecific Vasodilators.- IV. Antiplatelet Drugs.- V. Inhibitors of Thromboxane Synthesis and Thromboxane Antagonists.- VI. Defibrinating Agents, Fibrinolytics, and Anticoagulants.- D. Conclusions.- References.- 13 Biochemical Effects of Gerontopsychopharmacological Agents.- A. Introduction.- B. Pathobiochemical and Pathophysiological Variations of Brain Functions in Gerontopsychiatry: General Considerations.- C. Studies of Drug Effects in Gerontopsychiatric Patients.- I. Sympathicomimetic Drugs.- II. Sympathicolytic Agents.- III. Miscellaneous Vasoactive and Metabolically Active Drugs.- D. Concluding Remarks.- References.- Psychomotor Stimulants.- 14 The Pharmacological Profile of Some Psychomotor Stimulant Drugs Including Chemical, Neurophysiological, Biochemical, and Toxicological Aspects.- A. Introduction.- B. Chemistry.- C. Kinetics and Metabolism.- I. Amphetamine.- II. Methylphenidate.- III. Nomifensine.- IV. Mazindol.- V. Amineptine.- D. Interaction with Central Chemical Transmitters.- I. Catecholamines.- II. Serotonin.- III. Acetylcholine.- E. Pharmacology.- I. Anorexia.- II. Locomotor Stimulation.- III. Stereotypy.- F. Other Effects.- G. Tolerance.- H. Toxicology.- References.- 15 The Behavioral Pharmacology of Psychomotor Stimulant Drugs.- A. Unconditioned Behavior.- I. Effects of Psychomotor Stimulant Drugs on Motor Activity.- 1. Acute Effects.- 2. Chronic Effects.- II. Effects of Psychomotor Stimulant Drugs on Food and Water Intake.- 1. Acute Effects.- 2. Chronic Effects.- III. Effects of Psychomotor Stimulant Drugs on Aggression.- 1. Acute Effects.- 2. Chronic Effects.- B. Conditioned Behavior.- I. Effects of Psychomotor Stimulant Drugs on Schedule-Controlled Behavior.- 1. Acute Effects.- 2. Chronic Effects.- II. Stimulus Properties of Psychomotor Stimulant Drugs.- 1. Psychomotor Stimulant Drugs as Unconditioned Stimuli.- 2. Psychomotor Stimulant Drugs as Discriminative Stimuli.- 3. Psychomotor Stimulant Drugs as Reinforcing Stimuli.- C. General Comments.- References.- 16 The Dependence-Producing Properties of Psychomotor Stimulants.- A. Introduction.- B. Evolution of the Concepts of Dependence.- C. The Nature of Dependence and Pertinent Aspects of the Properties of Dependence-Producing Drugs.- D. Epidemiologic and Clinical Aspects of Dependence on Psychomotor Stimulants.- E. Methods for the Laboratory Study of Drug Self-Administration.- F. Self-Administration of Psychomotor Stimulants by Laboratory Animals.- I. Self-Administration Under Unlimited Drug Access.- II. Self-Administration Under Restricted Drug Access.- G. Chains of Behavior Maintained by Psychomotor Stimulants.- H. Quantitative Assessment of Reinforcing Properties.- I. Evaluation of Preference.- J. Progressive Ratios: Evaluation of the Maximum Behavioral Output Sustained by Self-Administration.- References.- Author Index.