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Antipsychotics and antidepressants

Author: M Ackenheil; G Stille; F Hoffmeister
Publisher: Berlin ; New York : Spirnger-Verlag, 1980.
Series: Psychotropic agents, pt. 1.; Handbook of experimental pharmacology, v. 55/I.
Edition/Format:   Print book : EnglishView all editions and formats
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Document Type: Book
All Authors / Contributors: M Ackenheil; G Stille; F Hoffmeister
ISBN: 0387098585 9780387098586 3540098585 9783540098584
OCLC Number: 6087550
Description: xxiv, 734 pages ; 25 cm.
Contents: Antipsychotics: Chemistry (Structure and Effectiveness).- 1 Tricyclic Neuroleptics: Structure-Activity Relationships.- A. Criteria for Neuroleptic Activity.- B. Chemical Classification of the Tricyclic Neuroleptics.- C. Molecular Conformation.- D. Stereospecificity of Action.- E. Nature of the Basic Side Chain.- F. Aromatic Substitution.- G. Nature of the Central Ring.- H. Non-Cataleptogenic Neuroleptics.- I. Conclusion.- References.- 2 Butyrophenones and Diphenylbutylpiperidines.- A. Introduction.- B. Structure-Activity Relationships.- I. Chemistry.- II. Pharmacology.- III. Clinical Aspects.- 1. Butyrophenones.- 2. Diphenylbutylpiperidines.- C. Conclusion.- References.- 3 Centrally Acting Rauwolfia Alkaloids.- A. Introduction and History.- B. Biologic Fate and Mechanisms of Action of Reserpine.- C. Central Actions of Reserpine.- I. Effect of Reserpine on Behavior.- II. Effect of Reserpine on the Motor System.- III. Effects of Reserpine on Bioelectric Signals.- D. Comparison with Other Neuroleptics.- I. General Clinical Effects.- II. Alleged Depression-Inducing Effect of Neuroleptics.- References.- 4 Behavioral Pharmacology of Antipsychotics.- A. Introduction.- B. Basic Aspects and Considerations in Regard to Investigations.- C. Action of Antipsychotics on Spontaneous Behavior.- I. Pattern of Action on Behavior.- II. Locomotion.- III. Immobilization.- IV. Muscle Relaxation and Ptosis.- V. Excitation Conditions.- VI. Aggression.- VII. Reproduction.- VIII. Maternal Behavior.- IX. Feeding Behavior.- X. Prey Catching.- XI. Memory and Learning.- D. Actions of Antipsychotics on Induced Behavioral Patterns.- I. Stimulant-Induced Excitation Patterns.- II. Tryptamine-Induced Convulsion.- III. Withdrawal Syndrome.- IV. Topical Brain Stimulation.- V. Self-Stimulation.- VI. Rotational Model.- VII. Brain Lesions.- E. Side-Effects Following Acute and Chronic Administration and Tolerance Phenomena.- F. Conclusions.- References.- 5 Testing Antipsychotic Drug Effects with Operant Behavioral Techniques.- A. General Advantages of Operant Procedures for the Demonstration of Behavioral Drug Effects.- B. Operant Procedures for Evaluating Antipsychotic Drug Actions.- I. Active Avoidance Tests.- II. Other Operant Procedures.- C. Value of Operant Techniques for Detecting Antipsychotic Drug Effects.- D. Summary.- References.- 6 Stereotyped Behavior and Its Relevance for Testing Neuroleptics.- A. Similarities and Differences Between Endogenous Psychoses and States Induced by Amphetamines in Man or Animals.- I. Amphetamine Psychosis and Endogenous Psychoses.- II. Comparison of Animal and Human Data.- B. Relevance of Stereotypies in Testing Antipsychotic Drugs.- References.- 7 Neurophysiologic Properties of Neuroleptic Agents in Animals.- A. Pre- and Postsynaptic Action of Antipsychotic Drugs.- B. Spinal Neurones and Descending Pathways.- C. Presence of Monoamines in the Brain Stem.- I. Arousal.- II. Analgesia and Nociceptive Reflexes.- III. Seizure Activity.- IV. Vomiting, Swallowing.- D. Nigro-Neostriatal System.- I. DA as a Transmitter.- II. The Neuronal Feedback Loop and Self-Inhibition.- III. Spinal Motor Activity.- E. Mesolimbic System.- F. Locus Coeruleus and Other Brain Stem Nuclei: Ascending Pathways.- G. Cyclic-AMP.- H. Concluding Remarks.- References.- 8 Antipsychotics: Neurophysiological Properties (in Man).- A. Future Prospects.- B. Summary.- References.- 9 Biochemical Effects of Neuroleptic Drugs.- A. Introduction.- B. General Biochemical Features of Neuroleptic Drugs.- C. Effects of Neuroleptic Drugs in Discrete Brain Structures.- I. Extrapyramidal System.- 1. Acetylcholine.- 2. GABA.- 3. Neuroleptic-Induced Feedback Activation of DA Neurons: Possible Role of ACh and GABA.- 4. Effects of Repeated Administration of Neuroleptics.- 5. Functional Correlates of Neuroleptic-Induced Biochemical Alterations.- II. Limbic System.- 1. Acetylcholine.- 2. GABA.- 3. Repeated Administration of Neuroleptics: Effects in Limbic System.- D. Atypical Neuroleptics.- References.- 10 Biochemical Effects (in Men).- A. Introduction.- B. Biochemical Findings in Urine.- C. Biochemical Findings in Blood.- D. Biochemical Findings in CSF.- E. Conclusions.- References.- 11 Toxicology of Antipsychotic Agents.- A. Introduction.- B. Butyrophenones.- I. General.- II. Animals.- 1. Acute Toxicity.- 2. Subchronic Toxicity.- 3. Chronic Toxicity.- 4. Fertility.- 5. Teratology.- 6. Perinatal and Postnatal Toxicity.- III. Human Subject.- 1. Acute Toxicity.- 2. Teratology.- 3. Perinatal and Postnatal Toxicity.- IV. Mutagenic Activity.- V. Discussion of Side-Effects.- C. Phenothiazines.- I. General.- II. Animal.- 1. Acute Toxicity.- 2. Subchronic Toxicity.- 3. Chronic Toxicity.- 4. Fertility.- 5. Teratology.- 6. Perinatal and Postnatal Toxicity.- III. Man.- 1. Acute Toxicity.- 2. Fertility.- 3. Teratology.- 4. Perinatal and Postnatal Toxicity.- IV. Mutagenic Activities.- V. Carcinogenicity.- VI. Physical Dependence.- VII. Discussion of Side-Effects.- D. Reserpine.- I. General.- II. Animals.- 1. Acute Toxicity.- 2. Subchronic Toxicity.- 3. Chronic Toxicity.- 4. Fertility.- 5. Teratology.- 6. Perinatal and Postnatal Toxicity.- III. Man.- 1. Acute Toxicity.- 2. Teratology.- 3. Perinatal and Postnatal Toxicity.- IV. Carcinogenicity.- V. Discussion of Side-Effects.- References.- 12 Clinical Pharmacology (Pharmacokinetics).- A. Introduction.- B. Phenothiazines and Thioxanthenes.- I. Chlorpromazine, Levomepromazine.- 1. Methods for Assessment of Chlorpromazine Concentration in Biological Fluids.- 2. Pharmacokinetics of CPZ in Man.- II. Phenothiazines with Piperidine Side-Chain (Thioridazine, Mesoridazine).- 1. Methods for Assessment of Thioridazine Concentration in Biological Fluids.- 2. Pharmacokinetics of Thioridazine and Mesoridazine in Man.- III. Phenothiazines with Piperazine Side-Chain (Perazine, Butaperazine, Perphenazine, Fluphenazine).- 1. Methods for Assessment of Plasma Concentrations.- 2. Pharmacokinetics of Piperazine Side-Chain Phenothiazines in Man.- IV. Pharmacokinetics of Thioxanthenes in Man.- C. Pharmacokinetics of Clozapine and Loxapine in Man.- D. Pharmacokinetics of Butyrophenones in Man.- References.- 13 Metabolism and Kinetics.- A. Introduction.- B. Phenothiazines and Thioxanthenes.- I. Kinetics in Animals.- 1. Absorption.- 2. Distribution.- 3. Elimination.- II. Extent of Biotransformation in Vivo.- III. Metabolic Pathways.- 1. Reactions at the Ring System.- 2. Reactions at the C-2 Substituent.- 3. Reactions at the N-10 Side Chain.- 4. Combinations of Reactions.- C. Clozapine.- I. Kinetics in Animals.- II. Metabolism.- D. Butyrophenones and Diphenylbutylpiperidine Derivatives.- I. Kinetics in Animals.- II. Metabolism.- E. Reserpine.- References.- 14 Psychometric and Psychophysiological Actions of Antipsychotics in Men.- A. Introduction.- I. Aims of the Review.- B. Methodological Problems in Measuring the Effects of Antipsychotic Drugs on Behavioral and Psychophysiological Parameters.- I. Selection of Indicators.- II. Selection of Situational Conditions.- III. Selection of Subjects.- IV. Time Course of Action.- C. Review of Antipsychotic Drugs on Different Areas of Psychological Functioning.- I. Effects of Antipsychotic Drugs on Perception.- 1. Assessment Approaches.- 2. Determination of Thresholds.- II. Effects of Antipsychotic Drugs on Thinking and Intelligence (Cognitive Processes).- 1. Assessment Approaches.- 2. General Intelligence Tests.- 3. Reasoning.- 4. Word Fluency.- 5. Verbal Thinking.- 6. Conclusions on the Effects of Antipsychotic Drugs on Cognitive Processes.- III. Learning.- 1. Assessment Aproaches.- 2. Verbal Learning.- 3. Classical Conditioning.- 4. Operant Conditioning.- 5. Conclusions Concerning the Effects of Antipsychotic Drugs on Learning.- IV. Memory Processes.- V. Effects of Antipsychotic Drugs on Psychomotor Performance.- 1. Assessment Approaches.- 2. Psychomotor Speed.- 3. Sensorimotor Speed.- 4. Complex Psychomotor and Sensory Coordination.- 5. Finger, Hand, and Arm Dexterity.- 6. Finger and Hand Steadiness.- 7. Precision of Small Movements of Fingers, Hands, and Arms.- 8. Other Types of Psychomotor Abilities.- 9. Conclusions About the Effects of Antipsychotic Drugs on Psychomotor Abilities.- VI. Concentration and Vigilance.- 1. Assessment Approaches.- 2. Vigilance.- 3. Concentration as Measured by Coding Tests (Digit Symbol Test).- 4. Concentration Measured by Continuous Arithmetic Calculations.- 5. Concentration Measured by Cancellation Tests.- 6. Conclusions Concerning the Effects of Antipsychotic Drugs on Concentration and Vigilance.- VII. Effects of Antipsychotic Drugs on Psychophysiological Parameters.- 1. Problems of Psychophysiological Measures.- 2. Measures of Central Nervous System.- 3. Autonomic Nervous System Measures.- VIII. Emotional Processes.- 1. Assessment Approaches.- 2. Emotional Stability.- 3. Anxiety.- IX. Motivational Processes.- 1. Assessment Approaches.- 2. Activation.- 3. Other Motivational Aspects.- References.- 15 Endocrine Effects of Neuroleptics.- A. History.- B. Psychotherapeutic Drugs Affecting the Endocrine System.- I. Phenothiazines.- II. Butyrophenones.- III. Rauwolfia Derivatives.- IV. Benzodiazepines.- V. Barbiturates.- VI. Lithium.- VII. Thalidomide.- VIII. Antidepressants.- IX. Hydroxyzine.- X. Ergot Derivatives.- C. Mechanisms of Endocrine Effects.- I. The Mediator Theory.- II. The Tropin Balance Theory.- III. The Steroid Receptor Theory.- D. Conclusions.- References.- Antidepressants: Chemistry (Structure and Effectiveness).- 16 Chemistry (Structure and Activity).- A. Thymoleptics.- I. Imipramine.- II. Imipramine Analogs.- III. Search for the "Active" Conformation of Imipramine and Its Analogs.- IV. Further Exploration of Structure-Activity Relationships.- V. Compounds Found in Screening.- VI. Search for Compounds with Greater Specificity.- VII. Compounds with a Mechanism of Action Different From that of Imipramine and Its Analogs.- B. Conclusion.- References.- 17 Monoamine Oxidase Inhibitors as Antidepressants.- A. Introduction.- B. Pharmacology - Background.- I. Pharmacology of MAOIs.- II. Function.- III. Structure and Biologic Action.- IV. Mode of Action.- V. MAOIs Used Clinically.- VI. Biochemical Markers - Usefulness in Practice.- VII. Acetylation Phenotype.- C. Evaluation of MAOI Antidepressant Efficacy.- I. Experimental Design Problem.- 1. Spontaneous Remission.- II. Controlled and Open Studies.- III. Time Lapse before Response.- D. Practicum for Clinical Use.- I. How to Select Patients for a MAOI.- II. Patient Compliance.- III. When to Use a Monoamine Oxidase Inhibitor.- IV. Secondary Causes of Depression.- V. Indications for the Monoamine Oxidase Inhibitors.- E. Use in Phobic Anxiety.- F. Achievers' Depression.- I. Posology.- II. Toxicity and Side Effects.- III. Interactions.- 1. With Tricyclic Antidepressants.- 2. With Narcotic Analgesics.- 3. With Insulin.- 4. With Other Prescription Medications.- 5. With Over-the-Counter Medications.- G. Potential for Drug Abuse.- I. Behavioral Toxicity.- H. Management of Overdosage and Side Effects.- I. Summary.- References.- 18 Tricyclic Antidepressants: General Pharmacology.- A. Introduction.- B. Behavioral Effects.- C. Interaction with Other Drugs.- D. Interaction with Biogenic Amines.- E. Amine Uptake Inhibition.- F. Cardiovascular Effects.- G. Concluding Remarks.- References.- 19 Neurophysiological Properties (in Animals).- A. Tricyclic Antidepressants (ADs).- I. Effects of ADs on the Electrical Activity of the Brain.- II. Actions of ADs on the Excitability of the CNS.- III. Action of ADs on the EEG Arousal Response.- IV. Drug-Interaction Studies on ADs.- V. Additional Neurophysiological Studies on the Effects of ADs.- B. Monoamine Oxidase Inhibitors (MAOIs).- I. Effects of MAOIs on the Electric Activity of the Brain.- II. Additional Neurophysiological Results on the Effects of MAOIs.- C. Concluding Remarks.- References.- Supplementary References.- 20 Clinical Neurophysiological Properties of Antidepressants.- A. Introduction.- B. EEG Classification of Psychotropic Drugs.- C. Method of EEG Analysis.- D. EEG Findings in Depression.- E. EEG Findings with Antidepressants.- I. Drugs Commonly Used as Antidepressants.- 1. Tricyclic Antidepressants.- 2. MAO Inhibitors.- 3. Inorganic Salts.- 4. Miscellaneous Antidepressants.- II. Drugs Belonging to Other Classes but Having Some Antidepressant Properties.- 1. Neuroleptics with Antidepressant Properties.- 2. Psychostimulants.- III. Drugs Predicted as Antidepressant Based on their CEEG Profiles.- 1. Drugs Predicted by Animal Pharmacology as Antidepressants, and Confirmed Based on CEEG Profiles.- 2. Drugs Predicted to be Antidepressants by CEEG Alone, But Not by Animal Pharmacology.- F. Summary and Conclusion.- References.- 21a Biochemical Effects of Antidepressants in Animals.- A. Introduction.- B. Monoamine Oxidase Inhibitors.- I. Multiple Forms of MAO and Selective MAO Inhibitors.- II. Physiologic Consequences of MAO Inhibition.- C. Tricyclic Antidepressants and Other Drugs Which Affect Monoaminergic Systems in Brain.- I. Effects of Tricyclic Antidepressants on MAO Activity.- II. Blockade by Tricyclic Antidepressants of the Uptake of Biogenic Amines.- III. Interaction of Tricyclic Antidepressants with Other Drugs.- IV. Effect of Tricyclic Antidepressants Following Their Prolonged Administration on Adaptive Presynaptic Regulation.- V. Miscellaneous Biochemical Effects of Antidepressant Drugs.- D. Effect of Antidepressant Drugs on the Sensitivity of the NE-Receptor-Coupled Cyclic AMP Generating System in the Limbic Forebrain and in Other Structures of the Brain.- References.- 21b Biochemical Effects of Antidepressants in Man.- A. General Introduction.- B. Biochemical Effects of Antidepressants as Reflected in the Urine.- I. Introduction.- II. Effects of Tricyclics and MAO Inhibitors.- III. Discussion.- C. Biochemical Effects of Antidepressants as Reflected in the Blood.- I. Introduction.- II. Effects of Tricyclics and MAO Inhibitors.- III. Discussion.- D. Biochemical Effects of Antidepressants as Reflected in the CSF.- I. Introduction.- II. Effects of Tricyclics, MAO Inhibitors, and Precursors of Biogenic Amines.- III. Discussion.- E. General Discussion.- References.- 21c Drug-Induced Alterations in Animal Behavior as a Tool for the Evaluation of Antidepressants: Correlation with Biochemical Effects.- A. Introduction.- B. Amine-Depleted Animals as a Model for the Study of Antidepressants, Correlations with Biochemical Effects.- I. Parameters Used for the Determination of Antidepressant Effects in Amine-Depleted Animals.- C. Drug-Induced Behaviors Implicating Aminergic Stimulation in the Evaluation of Antidepressants.- I. Behavioral Responses Induced by Indirect Stimulation of Catecholaminergic Receptors.- II. Behavioral Responses Induced by Direct Stimulation of Monoaminergic Receptors.- III. Behavioral Response Related to Serotoninergic Stimulation.- D. Final Conclusion and Remarks.- References.- 22 Toxicology of Antidepressant Drugs.- A. Introduction.- B. Monoamine Oxidase Inhibitor.- I. Animal Toxicity.- 1. General Toxicology.- 2. Interaction Experiments.- II. Intoxication in Man.- 1. Effects of Acute Overdose.- 2. Treatment of Acute MAO Inhibitor Overdose.- 3. Chronic Toxicity of MAO Inhibitors.- C. Tricyclic Antidepressants.- I. Animal Toxicity.- 1. General Toxicology.- 2. Interaction Experiments.- 3. Cardiovascular Effects.- 4. Induction of Myeloid Body Formation.- II. Teratology.- III. Intoxication in Man.- 1. Effects of Acute Overdose.- 2. Treatment of Tricyclic Antidepressant Overdose.- D. Conclusions.- References.- 23 Metabolism of Antidepressants.- A. Introduction.- B. Dibenzazepines.- I. Imipramine and Its Therapeutically Used Metabolites.- II. Derivatives of Imipramine.- 1. Chlorimipramine.- 2. Trimepramine.- 3. Lofepramine.- 4. Ketipramine.- C. Dibenzocycloheptadienes (Amitriptyline, Nortriptyline).- D. Other Antidepressants.- 1. Noxiptiline.- 2. Opipramol.- 3. Protriptyline.- 4. Proheptatriene.- 5. Intriptyline.- 6. Doxepine.- 7. Prothiadene.- 8. Melitracene.- 9. Dimethacrine.- 10. Maprotiline.- 11. Dibenzepine.- 12. Miscellaneous Antidepressants.- References.- 24 Physiological and Psychological Effects of Antidepressants in Man.- A. Introduction.- B. Central Physiological Effects.- C. Peripheral Physiological Effects.- I. Skin Conductance.- II. Finger Tremor.- III. Pupil Diameter.- IV. Cardiovascular Changes.- V. Salivation Rate.- D. Psychological Effects.- E. Conclusions.- References.- 25 Pharmacology and Toxicology of Lithium.- A. Human Data, Animal Data, in Vitro Data.- B. Pharmacokinetics.- C. Renal Elimination and Mechanism of Poisoning.- D. Adverse Effects.- I. Neuromuscular System.- II. Mind.- III. Heart.- IV. Thyroid.- V. Kidneys.- VI. Skin.- VII. Body Weight.- VIII. Edema.- E. Teratogenicity.- F. Lactation.- G. Interaction with Other Drugs.- H. Literature.- References.- 26 Antipsychotics and Experimental Seizure Models.- A. Introduction.- B. Neuroleptics.- I. Tricyclic Compounds.- 1. Clorpromazine.- 2. Other Tricyclic Neuroleptics.- II. Butyrophenos and Diphenylbutylpiperidines.- C. Reserpine.- D. Influence of Neuroleptics and Reserpine on the Effects of Anticonvulsant Drugs.- E. Conclusions.- References.- Author Index.
Series Title: Psychotropic agents, pt. 1.; Handbook of experimental pharmacology, v. 55/I.
Responsibility: contributors, M. Ackenheil [and others] ; editors, F. Hoffmeister, G. Stille.

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