Handbook of Psychopharmacology, Softcover reprint of the original 1st ed. 1978 Volume 13 Biology of Mood and Antianxiety Drugs

Underlying the design of the Handbook of Psychopharmacology is a prejudice that the study of drug influences on the mind has advanced to a stage where basic research and clinical application truly mesh. These later volumes of the Handbook are structured according to this conception. In certain volumes, groups of drugs are treated as classes with chapters ranging from basic chemistry to clinical application. Other volumes are assembled around topic areas such as anxiety or affective disorders. Thus, besides chapters on individual drug classes, we have included essays addressing broad areas such as "The Limbic-Hypothalamic-Pituitary-Adrenal System and Human Be­ havior" and "Peptides and the Central Nervous System. " Surveying these diverse contributions, one comes away with a sentiment that, far from being an "applied" science borrowing from fundamental brain chemistry and physiology, psychopharmacology has instead provided basic researchers with the tools and conceptual approaches which now are advancing neurobiology to a central role in modern biology. Especially gratifying is the sense that, while contributing to an understanding of how the brain functions, psychopharmacology is a discipline whose fruits offer genuine help to the mentally ill with promises of escalating benefits in the future. L. L. 1. S. D. 1. S. H. S. vii CONTENTS CHAPTER 1 Peptides and the Central Nervous System ARTHUR]. PRANGE, ]R. , CHARLES B. NEMEROFF, MORRIS A. LIPTON, GEORGE R. BREESE, and IAN C. WILSON 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Hypothalamic Releasing Hormones: Animal Studies. . . . . 2 2. 1. Thyrotropin-Releasing Hormone (TRH, Thyroliberin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 Peptides and the Central Nervous System.- 1. Introduction.- 2. Hypothalamic Releasing Hormones: Animal Studies.- 2.1. Thyrotropin-Releasing Hormone (TRH, Thyroliberin).- 2.2. Pro-Leu-Gly-NH2 (PLG, MIF-I).- 2.3. Luteinizing Hormone-Releasing Hormone (LHRH, Gonadoliberin).- 2.4. Somatotropin Release-Inhibiting Factor (SRIF, Somatostatin).- 3. Pituitary Peptide Hormones: Animal Studies.- 3.1. Anterior Pituitary Hormones: Corticotropin-Related Peptides (MSH, ACTH, LPH).- 3.2. Anterior Pituitary Hormones: Glycoprotein Hormones (LH, FSH, TSH, CG).- 3.3. Anterior Pituitary Hormones: Somatomammotropins (GH, PRL, CS).- 3.4. Posterior Pituitary Hormones.- 4. Other Brain Peptides: Animal Studies.- 4.1. Angiotensin II (Angiotensin).- 4.2. Cholecystokinin (CCK, Pancreozymin).- 4.3. Substance P.- 4.4. Bradykinin (Kinin-9).- 4.5. Neurotensin.- 4.6. Sleep-Inducing Peptides.- 4.7. Learning-Related Peptides.- 4.8. Morphine-like Peptides.- 4.9. Dipeptides.- 4.10. Other Peptides.- 5. Hypothalamic Releasing Hormones: Human Studies.- 5.1. Introduction.- 5.2. Thyrotropin-Releasing Hormone.- 5.3. Pro-Leu-Gly-NH2.- 5.4. Luteinizing Hormone-Releasing Hormone.- 6. Pituitary Peptide Hormones: Human Studies.- 6.1. Anterior Pituitary Hormones.- 6.2. Posterior Pituitary Hormones.- 7. Discussion.- 8. References.- 2 The Limbic-Hypothalamic-Pituitary-Adrenal System and Human Behavior.- 1. Introduction.- 2. Description of the Limbic-Hypothalamic-Pituitary-Adrenal System.- 2.1. Brief Outline.- 2.2. Description of LHPA Subunits.- 3. Procedures for Evaluating LHPA Function in Humans.- 3.1. Study of Neuronal Regulatory Mechanisms.- 3.2. Tissue Exposure to ACTH/Cortisol.- 3.3. General Methodologic Issues.- 3.4. Psychotropic Drug Effects on LHPA Function.- 4. Relationship between Mental Phenomena and the LHPA System.- 4.1. Behavioral Abnormalities in Patients with Disorders of the LHPA System.- 4.2. LHPA Function in Psychiatric Disorders.- 5. Summary.- 6. References.- 3 Approaches to Brain Amines in Psychiatric Patients: A Reevaluation of Cerebrospinal Fluid Studies.- 1. Introduction.- 1.1. Purpose.- 1.2. Amine Hypotheses of Affective Illness and Schizophrenia.- 2. Methodological Considerations for Spinal Fluid Studies.- 2.1. Origins of Amine Metabolites.- 2.2. The Probenecid Technique.- 2.3. Clinical Methodology.- 3. CSF Amine Metabolites in Affective Illness.- 4. Amine Metabolism in Schizophrenic Patients.- 5. Pharmacological Approaches: Integration with Amine Metabolite Data.- 5.1. Amine Precursor Strategies.- 5.2. Inhibitors of Amine Synthesis.- 5.3. Newer Amine-Receptor Stimulators and Implications.- 5.4. Amine Alterations Associated with “Routine” Antidepressant Treatments.- 5.5. Neuroleptic Treatments: Implications for the Dopamine Hypothesis.- 5.6. Psychotogenic Agents.- 6. Theoretical Overview: The Question of Specificity.- 6.1. Relationship of Metabolite Data to Amine Theories.- 6.2. Implications of Parkinson’s Disease Model.- 6.3. Drug-Metabolite Interactions: Contributions to Amine Theories.- 7. A Model for Defects in Compensatory and Regulatory Mechanisms.- 8. References.- 4 Amine Hypotheses of Affective Disorders.- 1. Introduction.- 2. Classification of Depressions.- 2.1. Multidimensional Diagnosis of Depressions.- 2.2. Syndromal Points of View.- 2.3. Etiological Points of View.- 2.4. Classification According to Course.- 2.5. Pathogenetic Points of View.- 2.6. Other Diagnostic Classifications.- 2.7. Conclusions.- 3. Serotonin Metabolism in Affective Disorders: Study of Peripheral Indicators.- 3.1. Urinary Excretion of Indoleamines.- 3.2. 5-HT Synthesis.- 3.3. Availability of Tryptophan.- 3.4. Conclusions.- 4. Metabolism of Catecholamines in Affective Disorders: Study of Peripheral Indicators.- 4.1. Catecholamines and Some of Their Metabolites in Urine and Blood.- 4.2. Urinary MHPG Excretion: A Peripheral Indicator of Central Noradrenaline Activity?.- 4.3. Tyrosine in Blood.- 4.4. Enzyme Studies.- 4.5. Neuroendocrine Factors as “Markers” of Catecholaminergic Activity.- 4.6. Cyclic AMP and Central Catecholaminergic Activity.- 4.7. Conclusions.- 5. Postmortem Study of Central Monoamine Metabolism in Depressions.- 5.1. Introduction.- 5.2. Indoleamines.- 5.3. Catecholamines.- 5.4. Monoamine Oxidase.- 5.5. Significance of Postmortem Findings.- 5.6. Conclusions.- 6. Central Monoamine Metabolism in Affective Disorders: CSF Studies Without Probenecid.- 6.1. Monoamine Metabolites in CSF: Do They Reflect Central Monoamine Metabolism?.- 6.2. Monoamine Metabolites in Lumbar CSF: Do They Reflect Cerebral or Spinal Monoamine Metabolism?..- 6.3. Shortcomings of the CSF Strategy.- 6.4. Monoamine Metabolites in the CSF in Affective Disorders.- 6.5. Causes of the Variability of the Results of CSF Studies.- 6.6. Are the CSF Changes Syndrome-Dependent or Syndrome-Independent?.- 6.7. Specificity of CSF Findings.- 6.8. Ability of the CNS to Synthesize Monoamines.- 6.9. Conclusions.- 7. Central Monoamine Metabolism in Affective Disorders: CSF Studies After Probenecid Loading.- 7.1. Principles of the Probenecid Technique.- 7.2. Advantages of the Probenecid Technique over “Plain” CSF Determination.- 7.3. Procedure of the Probenecid Test.- 7.4. Does the Probenecid Technique Afford Information on Human Dopamine and 5-HT Turnover?.- 7.5. Shortcomings of the Probenecid Technique.- 7.6. Central 5-HT Turnover in Depressions.- 7.7. Central Dopamine Turnover in Depressions.- 7.8. Central 5-HT and Dopamine Turnover in Mania.- 7.9. Selectivity of the Probenecid Findings.- 7.10. Are the Disorders of 5-HT and Dopamine Metabolism Syndrome-Dependent or Syndrome-Independent?.- 7.11.Conclusions.- 8. Verification of the Monoamine Hypothesis with the Aid of Drugs: I. Monoamine Precursors and Synthesis Inhibitors.- 8.1. Justification of the Strategy.- 8.2. Studies with Drugs Which Increase 5-HT Synthesis.- 8.3. Studies with Drugs Which Increase Catecholamine Synthesis.- 8.4. Imperfections of the Precursor Strategy.- 8.5. Studies with Drugs Which Inhibit Monoamine Synthesis.- 8.6. Conclusions.- 9. Verification of the Monoamine Hypothesis with the Aid of Drugs and Other Methods of Antidepressant Therapy: II. Direct Influencing of the Transmission Process.- 9.1. Disorders in Central Monoamine Metabolism and Therapeutic Efficacy of Antidepressants.- 9.2. Tricyclic Antidepressants Combined with MAOIs.- 9.3. MAOIs Combined with Reserpine.- 9.4. Tricyclic Antidepressants and Central Stimulants.- 9.5. Tricyclic Antidepressants Combined with Reserpine..- 9.6. Enhancement of Central 5-HT Activity with the Aid of Chloramphetamines.- 9.7. Thyrotropin-Releasing Hormone.- 9.8. Neuroleptics and ?-Blockers.- 9.9. Methysergide.- 9.10. Lithium.- 9.11. Electroconvulsive Therapy.- 9.12. Conclusions.- 10. Theories to Explain the Monoamine Deficiency in Depressions.- 10.1. Possible Causes of the Monoamine Deficiency.- 10.2. Precursor Deficiency.- 10.3. Diminished Synthetic Capacity.- 10.4. Postsynaptic Defects.- 10.5. Conclusions.- 11. Preliminaries to Expansion of the Monoamine Hypothesis 270 11.1 Acetylcholine.- 11.2. Phenylethylamine.- 11.3. Conclusions.- 12. General Conclusions.- 13. References.- 5 Clinical Pharmacokinetics of Selected Psychotropic Drugs.- 1. Introduction.- 2. Tricyclic Antidepressants.- 2.1. Absorption.- 2.2. Steady-State Plasma Levels.- 2.3. Distribution.- 2.4. Volume of Distribution.- 2.5. Plasma Protein Binding.- 2.6. Biotransformation.- 2.7. Pharmacokinetics and Therapeutic Response.- 3. Lithium.- 3.1. Absorption, Doses, and Plasma Levels.- 3.2. Distribution.- 3.3. RBC/Plasma Lithium Ratio.- 3.4. Excretion.- 3.5. General Considerations.- 4. Benzodiazepines.- 4.1. Diazepam.- 4.2. Chlordiazepoxide.- 5. CNS Stimulants (Amphetamine).- 5.1. Absorption.- 5.2. Distribution.- 5.3. Metabolism and Excretion.- 5.4. Pharmacokinetics and Drug Response.- 6. Chlorpromazine.- 6.1. Absorption.- 6.2. Distribution.- 6.3. Metabolism and Excretion.- 6.4. Plasma Levels of Chlorpromazine and Metabolites.- 6.5. Plasma Levels and Clinical Correlates.- 7. Conclusion.- 8. References.- 6 Behavioral Pharmacology of Antianxiety Drugs.- 1. Introduction.- 2. Anticonflict Properties of Antianxiety Agents.- 2.1. Validity of Conflict Methodology.- 2.2. Separation between Effective and Ineffective Agents..- 2.3. Exceptions to Anticonflict Generalizations.- 2.4. Species Generality of Conflict Methodology.- 2.5. Studies with Drug-Naïve Animals.- 2.6. Biochemical Hypotheses of the Mechanisms of Action of Antianxiety Agents.- 2.7. Anxiety and ?-Blockade.- 3. Properties of Antianxiety Agents in Miscellaneous Operant Conditioning Situations.- 4. Properties of Antianxiety Agents in Additional Behavioral Procedures.- 4.1. Unpunished Consummatory Behavior: Appetite-Enhancing Effects.- 4.2. Punished Consummatory Behavior.- 4.3 Unpunished Exploratory and Locomotor Behavior.- 4.4. Punished Exploratory and Locomotor Behavior.- 4.5. Protection Against the Effects of Stress.- 5. Concluding Remarks.- 6. References.- 7 Antianxiety Drugs: Clinical Use in Psychiatry.- 1. Introduction.- 2. Using Drugs to Treat Anxiety.- 2.1. What Is Anxiety?.- 2.2. How Drugs May Be Used to Alleviate Anxiety.- 2.3. Pharmacological Actions of Antianxiety Drugs.- 2.4. Drugs Used in the Treatment of Anxiety.- 2.5. Side Effects of Antianxiety Agents.- 2.6. Tolerance, Habituation, and Addiction with Antianxiety Agents.- 2.7. Minor Tranquilizers and Barbiturates.- 2.8. Diazepam vs. Chlordiazepoxide.- 2.9. Why Physicians Should Employ the Most Effective Antianxiety Agents.- 3. Improving Specific Symptom Profiles of Anxious Patients.- 3.1. Presenting Symptomatology.- 3.2. Improvement Levels Observed in Drug-Treated Anxious Patients.- 3.3. Effect of Antianxiety Agents on Specific Symptoms.- 3.4. Initial Symptom Severity, Duration of Illness, and Clinical Improvement.- 3.5. Implications of Present Findings for Appropriate Use of Antianxiety Agents.- 4. Predicting Improvement in Anxious Patients.- 4.1. Nonspecific Factors Affecting Improvement.- 4.2. Predicting Improvement with the Benzodiazepines.- 4.3. Physician’s Prognosis for Antianxiety Drug-Treatment Response.- 5. Conclusion.- 6. References.