Handbook of Psychopharmacology, 1978 Volume 14 Affective Disorders: Drug Actions in Animals and Man

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. VB CONTENTS CHAPTER 1 Monoamine Oxidase Inhibitors: Animal Pharmacology RICHARD F. SQUIRES 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. 1. Localization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. 2. Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1. 3. Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. Inhibition of 5-HT and Catecholamine Synthesis. . . . . . . . 5 3. Inhibition of Spontaneous Firing of 5-HT Neurons. . . . . .

1 Monoamine Oxidase Inhibitors: Animal Pharmacology.- 1. Introduction.- 1.1. Localization.- 1.2. Function.- 1.3. Mechanisms.- 2. Inhibition of 5-HT and Catecholamine Synthesis.- 3. Inhibition of Spontaneous Firing of 5-HT Neurons.- 4. Inhibitory Effects on Paradoxical Sleep and Pontogeniculooccipital Waves.- 5. Effects on Growth and Development.- 6. Inhibition of Ovulation.- 7. Effects on Lordosis.- 8. Effects on Male Copulatory Behavior.- 9. 5-HT-Dependent Behavioral Syndromes.- 9.1. MAOI plus Reserpine or Tetrabenazine.- 9.2. MAOI plus L-Tryptophan.- 9.3. MAOI plus 5-HTP.- 9.4. MAOI plus 5-HT-Uptake Inhibitor.- 10. Potentiation of Indoleamine Hallucinogens.- 11. Tryptamine Potentiation.- 12. Potentiation of Phenethylamine Hallucinogens.- 13. Hypotensive Effects.- 13.1. The False-Transmitter Hypothesis.- 13.2. Centrally Mediated Reduction of Blood Pressure.- 14. Tyramine Potentiation.- 15. Interactions of the MAOIs with Reserpine and Tetrabenazine.- 16. Anticonvulsant Actions of MAOIs.- 16.1. Electroshock and Metrazol Convulsions.- 16.2. Audiogenic Seizures.- 16.3. Other Types of Seizures.- 16.4. Conclusions.- 17. References.- 2 Monoamine Oxidase, Monoamine-Oxidase-Inhibiting Drugs, and Human Behavior.- 1. Introduction.- 2. MAO-Inhibiting Drugs: Biologic, Physiologic, and Behavioral Effects in Man.- 2.1. Monoamine Changes during MAO-Inhibitor Administration to Man.- 2.2. Physiological Changes during MAO-Inhibitor Treatment.- 2.3. Behavioral Changes during MAO-Inhibitor Administration to Man.- 3. Monoamine Oxidase in Human Brain and Other Tissues.- 4. Human Platelet Monoamine Oxidase.- 4.1. Characteristics of Human Platelet Monoamine Oxidase.- 4.2. Genetic Basis for Individual Differences in Platelet MAO Activity.- 4.3. Factors Influencing Platelet MAO Activity.- 4.4. Drug Effects on Platelet MAO Activity.- 4.5. Associations between Platelet MAO Activity and Various Human Disorders.- 5. Possible Association between Platelet MAO Activity and General Personality and Behavioral Factors.- 6. References.- 3 Tricyclic and Monoamine Oxidase Inhibitor Antidepressants: Structure-Activity Relationships.- 1. Introduction.- 1.1. Background.- 1.2. Purposes of this Review and a Limitation.- 2. Tricyclic and Related Compounds.- 2.1. Neuronal Membrane Mechanisms for the Uptake of Biogenic Amines.- 2.2. Inhibition of Norepinephrine Uptake.- 2.3. Inhibition of Catecholamine Uptake into Dopaminergic Neurons.- 2.4. Inhibition of Serotonin Uptake.- 2.5. Relationship between Inhibition of the Uptake of Biogenic Amines and Antidepressant Activity In Vivo : Influence of Structural Modifications.- 3. Monoamine Oxidase Inhibitors.- 3.1. The Active Site of Monoamine Oxidase.- 3.2. Structure-Activity Relationships among Substrates of Monoamine Oxidase.- 3.3. Multiple Substrate-Binding Sites.- 3.4. General Structural Requirements for Monoamine Oxidase Inhibition.- 3.5. Structure-Activity Relationships among Inhibitors of Monoamine Oxidase.- 4. MAOIs as Inhibitors of the Uptake of Biogenic Amines and Tricyclic Compounds as Inhibitors of Monoamine Oxidase.- 4.1. MAOIs as Inhibitors of Amine Uptake.- 4.2. Tricyclic Compounds as MAOIs.- 5. Summary and Perspective.- 6. References.- 4 Tricyclic Antidepressants: Animal Pharmacology (Biochemical and Metabolic Aspects).- 1. Introduction.- 2. Pharmacologic Test Procedures Predicting Clinical Antidepressant Activity.- 2.1. Potentiation of Exogenous and Endogenous Catecholamines at Peripheral Adrenergic Receptor Sites.- 2.2. Potentiation of Various Central Effects Elicited by Amphetamine-like Drugs.- 2.3. Antagonism of Guanethidine-Induced Catecholamine Depletion and Adrenergic Neuron Blockade.- 2.4. Antagonism of the Reserpine-like Syndrome in Rodents.- 2.5. Blockade by Tricyclic Antidepressants of the Uptake of Catecholamines and/or 5-HT.- 3. Mode of Interaction of Tricyclic Antidepressants with Adrenergic Mechanisms.- 4. Interaction of Tricyclic Antidepressants with Other Drugs.- 5. Effect of Tricyclic Antidepressants on Adaptive Regulation at Pre- and Postsynaptic Sites.- 6. Metabolic Fate of Tricyclic Antidepressants.- 7. Some General Considerations on iV-Demethylation of Tricyclic Antidepressants.- 8. Miscellaneous Pharmacologic Effects of Tricyclic Antidepressants.- 9. References.- 5 Tricyclic and Monoamine-Oxidase-Inhibitor Antidepressants: Clinical Use.- 1. Introduction.- 2. Tricyclic Antidepressants: Clinical Studies.- 3. Adverse Effects of Tricyclic Antidepressants.- 4. MAOI: Clinical Studies.- 5. Adverse Effects of the MAOIs.- 6. Treatment of the Acute Episode.- 7. Prophylaxis.- 8. Interactive Effects of Tricyclic Agents and Sociotherapy.- 9. Combined Drug Treatments.- 10. Other Uses of the Antidepressants.- 10.1. Neurotic Disorders.- 10.2. Antidepressants in the So-Called Psychosomatic Disorders.- 10.3. Narcolepsy.- 10.4. Disorders of Childhood.- 10.5. Phobia.- 10.6. Hyperactivity.- 10.7. Enuresis.- 11. Current Practices and Future Needs.- 12. References.- 6 Lithium Pharmacology and Physiology.- 1. Introduction.- 2. Historical Review.- 2.1. Discovery in Basic Chemistry.- 2.2. History of Clinical Uses.- 2.3. Present Uses.- 3. Basic Chemistry and Biophysics.- 3.1. Basic Properties.- 3.2. Lithium and Cell Membranes.- 3.3. Lithium and. Facilitated Diffusion.- 3.4. Lithium and Active Transport.- 4. Mechanism of Action.- 4.1. Intracellular Concentration.- 4.2. Lithium Adenylate Cyclase and Cyclic Adenosine 3?,5?-Phosphate (cAMP).- 4.3. Cellular Magnesium and Calcium.- 4.4. Synaptic Release and Synthesis of Catecholamines.- 4.5. Indoleamines and Lithium.- 4.6. Effect of Lithium on Acetylcholine.- 4.7. Lithium and GABA.- 4.8. Lithium and the Electrolyte/Membrane Theory of Affective Disorders.- 4.9. Integration of the Mechanisms of Action of Lithium and the Theories of Affective Disorders.- 5. Physiology.- 5.1. Absorption.- 5.2. Distribution.- 5.3. Excretion.- 5.4. Interactions with Other Cations.- 6. Interactions with Pharmaceuticals.- 6.1. Concurrent Use of Diuretics.- 6.2. Lithium and Haloperidol.- 6.3. Lithium and Insulin.- 6.4. Lithium and Tricyclic Antidepressants.- 6.5. Lithium and the MAOI-Tranylcypromine.- 6.6. Lithium and Diphenylhydantoin.- 7. Effects on Clinical Tests.- 7.1. ECG(EKG).- 7.2. EEG.- 7.3. WBC.- 7.4. Serum Sodium and Potassium.- 7.5. Serum Magnesium and Calcium.- 8. Conclusion.- 9. References.- 7 Lithium: Clinical Considerations.- 1. Introduction.- 1.1. Indications.- 2. Lithium in Mania.- 2.1. Uncontrolled and Single-Blind Studies.- 2.2. Controlled Studies.- 3. Lithium in Acute Endogenous Depression.- 4. Use of Lithium in Psychiatric Disorders Other Than Mania or Depression.- 4.1. Lithium In Tardive Dyskinesia.- 5. Use of Lithium in Disorders of Childhood and Adolescence.- 5.1. Hyperactive Children.- 5.2. Mood Disorders.- 6. Preparations, Dosage, and Control.- 6.1. Preparations.- 6.2. Stabilization of a Manic Episode.- 6.3. Maintenance Treatment.- 7. Toxicology of the Lithium Ion.- 7.1. Mild-Moderate Toxic Side Effects: Minor Lithium Intolerance.- 7.2. Lithium Poisoning.- 7.3. Treatment of Lithium Poisoning.- 7.4. General Considerations.- 7.5. Complications of Lithium Treatment.- 7.6. Neurological Side Effects of Lithium Maintenance.- 7.7. “Irreversible” Lithium Toxicity.- 8. References.- 8 Lithium Prophylaxis and Experimental Rubidium Therapy in Affective Disorders.- 1. Factors in Assessing Prophylaxis.- 2. Methodology of Prophylactic Trials.- 3. Early Trials.- 4. Double-Blind Trials.- 5. Prophylaxis in Depression.- 6. Considerations in Prophylaxis: Summary.- 7. The life Table.- 8. Rubidium in Psychiatry.- 9. Recent Studies.- 10. Endogenous Rubidium.- 11. Chronic Administration.- 12. Rubidium-Lithium Interactions.- 13. A Membrane Transport Hypothesis.- 14. References.