Psychotropic Agents

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.