Psychotropic Agents

Psychotomimetics.- 1 Chemistry of Psychotomimetics.- A. Introduction.- I. Terminology.- II. Methods of Assay.- III. Classification.- B. Psychotomimetics Structurally Related to Serotonin.- I. Indoles.- 1. Nitrogen-Substituted Tryptamine Derivatives.- 2. Ring-Substituted Tryptamine Derivatives.- II. Beta-Carbolines.- III. Ergot-Related Drugs.- 1. Synthetic Lysergic Acid Derivatives.- 2. Natural Lysergic Acid Derivatives.- C. Psychotomimetics Structurally Related to Dopamine.- I. Phenethylamines.- II. Phenylisopropylamines.- D. Psychotomimetics Structurally Related to Acetylcholine: Atropine-Related Drugs.- E. Miscellaneous Psychotomimetics.- I. Ibotenic Acid.- II. Dissociative Anesthetics.- III. Ibogaine.- IV. Kavakava.- V. Marihuana.- References.- 2 Pharmacology and Toxicology of Psychotomimetics.- A. Introduction.- B. Definition of a Psychotomimetic Drug.- C. Types of Psychotomimetics.- D. Epidemiologic Aspects.- E. The LSD-Mescaline-Psilocybin Group.- I. Chemistry.- II. Pharmacology.- III. Clinical Effects.- IV. Adverse Effects.- F. Harmine Alkaloids and Piperidyl Benzilates.- G. Phencyclidine.- I. History.- II. Chemistry.- III. Pharmacology.- IV. Clinical Effects.- V. Overdoses.- H. Conclusions.- References.- 3 Psychotomimetics: Behavioral Pharmacology.- A. Introduction.- B. The Behavioral Pharmacology of LSD and Related Compounds.- I. Operant (Instrumental) Behavior.- 1. Positive Reinforcement: Schedule-Controlled Behavior.- 2. Negative Reinforcement: Escape and Avoidance Behavior.- II. Respondent (Pavlovian) Behavior.- 1. Appetitive Conditioning.- 2. Aversive (Defense) Conditioning.- III. Perceptual Effects.- IV. Tolerance and Related Phenomena.- 1. Tolerance.- 2. Cross-Tolerance.- 3. Dependence.- V. Stimulus Properties of Psychotomimetics.- 1. Discriminative Stimulus Properties.- 2. Reinforcing Properties.- 3. Unconditioned Stimulus Properties.- C. Summary and Conclusions.- References.- 4 Biochemical Pharmacology of Psychotomimetics.- A. Introduction.- B. Effects in Man.- C. 5-HT and LSD.- I. The First 60 min.- II. Beyond 60 min.- III. LSD-5 HT Summary.- D. Other Psychotomimetics.- E. LSD and Catecholamines.- F. Lisuride and LSD.- G. Tolerance, Blockade, and Enhancement of LSD Effects.- H. Adenylate Cyclase.- I. Stereospecific Binding.- J. Conclusion.- References.- 5 Neurophysiology Properties of Psychotomimetics.- A. Introduction.- B. Psychotomimetic Drugs and Related Neurotransmitters.- I. Psychedelics.- 1. LSD and the Simple Indoleamines.- 2. Mescaline and Methoxyamphetamines.- II. Stimulants.- 1. Comparison of Amphetamine Isomers on the Activity of NE and DA Neurons.- 2. Differential Actions of Amphetamine Isomers on Striatal and Non-striatal DA Systems.- III. Deliriants.- 1. Antimuscarinic Drugs and Central Cholinergic Pathways.- 2. Action of Physostigmine in Cholinergic Pathways.- 3. Deliriants as a Model for Human Memory Disorders.- C. General Conclusions.- I. Stimulants.- II. Deliriants.- III. Psychedelic Drugs.- References.- 6 Dependence-Producing Liability of LSD and Similar Psychotomimetics.- A. Introduction: Definition of Drug Dependence.- B. Discovery of and Effects of LSD.- C. Problems in Assessing Dependence-Producing Liability.- D. Social Factors and the Dependence-Producing Liability of LSD.- E. Summary and Conclusions.- References.- Cannabis.- 7 Chemistry of Cannabis.- A. Introduction.- B. Naturally Occurring Cannabinoids.- I. Isolation and Structure.- II. Chemical Properties.- III. Syntheses.- C. Structure-Activity Relationships (SARs).- D. Cannabinoid Analysis.- E. Cannabinoid Metabolites.- F. Concluding Remarks.- References.- 8 Pharmacology and Toxicology of Cannabis.- A. Introduction.- B. Pharmacokinetic Effects.- I. Absorption.- II. Distribution.- III. Elimination.- C. Pharmacodynamic Effects.- I. In Information-Bearing Macromolecules.- II. In Functional Macromolecules.- III. In Functional Systems.- 1. Neurotransmission.- 2. Cardiovascular and Respiratory Systems.- 3. Food Consumption and Temperature Regulation.- 4. Analgetic and Anticonvulsant Effects.- 5. Motor System, Psychomotor Performance Tasks, and EEG.- D. Aspects of Tolerance.- E. Interactions with Other Drugs.- F. Conclusion.- References.- Alcohol.- 9 General Pharmacology and Toxicology of Alcohol.- A. Introduction.- B. General Pharmacology.- I. Absorption.- II. Distribution.- III. Metabolism.- IV. Excretion.- V. Mechanism of Action.- VI. Central Nervous System.- VII. Cardiovascular System.- VIII. Skeletal Muscles.- IX. Gastrointestinal Tract.- X. Miscellaneous.- XI. Tolerance.- C. Interaction of Ethanol and Other Drugs.- I. General Remarks.- II. Interaction of Alcohol with Psychotropic Drugs.- III. Interaction of Alcohol with Nonpsychotropic Drugs.- References.- 10 Behavioral Pharmacology of Alcohol.- A. Introduction.- B. Issues in Measurement and Interpretation.- I. Methodological Issues Specific to Alcohol Studies.- 1. Blood Alcohol Level Measurement.- 2. Alcohol Absorption.- 3. Alcohol Distribution.- 4. Alcohol Metabolism.- II. General Problems of Experimental Design.- 1. Baseline Assessments.- 2. Sex and Menstrual Cycle Phase.- 3. Expectancy About Drug Effects.- 4. Motivation to Perform.- 5. Attention to the Task.- 6. Patterns of Alcohol Administration.- III. Route of Alcohol Administration.- IV. Implications of Behavioral Tolerance.- V. Operational Definitions.- C. Clinical Studies of Alcohol Effects.- I. Alcohol and Mood.- II. Alcohol and Aggression.- III. Alcohol and Sexuality.- IV. Alcohol and Tension.- V. Alcohol and Sociability.- VI. Implications for Analysis of the Reinforcing Properties of Alcohol.- D. Behavioral Studies of Alcohol in Animal Models.- I. Animal Models of Alcohol Addiction.- II. Behavioral Studies of Alcohol Reinforcement.- 1. Effects of Alcohol Dose Per Injection on Alcohol Self-Administration Patterns.- 2. Effects of Saline Substitution.- 3. Effects of Alcohol Pretreatment on Alcohol Self-Administration Patterns.- 4. Effects of Duration of Alcohol Access on Alcohol Self-Administration.- E. Conclusions.- References.- 11 Biochemical Pharmacology of Alcohol.- A. Introduction.- B. Physical and Chemical Properties of Ethanol.- C. Peripheral Actions of Ethanol Having Indirect Effects in the Brain.- D. Pharmacologic Effects and Mechanisms of Ethanol Action in the Brain.- I. Effects on Oxidative Metabolism.- II. Effects on Ribonucleic Acid and Protein Synthesis.- III. Effects on Neurotransmitters.- 1. Biogenic Amines.- 2. Acetylcholine.- 3. Amino Acids.- IV. Effects on Membranes.- 1. Fluidity.- 2. Lipids.- 3. Sodium- and Potassium-Dependent Adenosine Triphosphatase.- 4. Calcium.- 5. Cyclic Nucleotides and Membrane Receptors.- V. Aldehyde-Biogenic Amine Cyclization Products.- E. Conclusion.- References.- 12 Dependence-Producing Effects and Alcohol Dependence Syndrome.- A. Introduction.- B. The Concept of Alcoholism.- C. Etiology of Alcoholism.- I. Genetic Hypotheses.- II. Psychological Hypotheses.- 1. Alcohol Effect Hypotheses.- 2. Learning Theory Hypotheses.- 3. Personality Hypotheses.- 4. Other Hypotheses.- III. Sociological Hypotheses.- 1. Universal Hypotheses.- 2. Cultural Hypotheses.- 3. Alienation Hypotheses.- 4. Subcultural Hypotheses.- D. Alcohol Dependence Syndrome.- I. Animal Models for Physical Dependence on Ethanol.- E. Chronic Effects of Alcohol Use.- I. Hepatotoxic Effects.- II. Pancreatotoxic Effects.- III. Brain Damage.- IV. Cardiotoxic Effects.- E. Epidemiology of Alcohol Use and Overuse.- G. Alcohol-Related Criminality.- H. The Treatment of Alcoholism.- I. Current Methods of Treatment.- II. Referral for Treatment.- III. Treatment Facilities.- 1. General Hospitals.- 2. Mental Hospitals.- 3. Detoxification Centers.- 4. Transitional Facilities.- 5. Alcoholics Anonymous.- 6. Pharmacological Methods in the Treatment of Alcohol Dependence Syndrome.- References.- Psychotropic Effects of Central Acting Drugs.- 13 Psychotropic Effects of Opioids and Opioid Antagonists.- A. Introduction.- B. Evaluation of Signs, Symptoms, and Subjective Effects in Humans.- I. Introduction.- II. Opioid Analgesics.- 1. Effects of Single Doses in Nondependent Subjects.- 2. Effects in Tolerant Subjects.- 3. Opioid Analgesics of Low Abuse Liability.- 4. Dextrorphan and Dextromethorphan.- 5. Subject Population.- III. Partial Agonists of the Morphine Type.- 1. Profadol and Propiram.- 2. Buprenorphine.- IV. Pentazocine-Like Opioids.- 1. Effects of Acute Doses.- 2. Chronic Administration.- V. Nalorphine- and Cyclazocine-Like Antagonists.- 1. Effects of Acute Doses.- 2. Chronic Administration.- VI. Naloxone and Naltrexone.- VII. Discussion.- 1. Quantitative Evaluation of Subjective Effects.- 2. Evaluation of Morphine-Like Abuse Liability.- 3. Psychotomimetic Effects.- 4. Barbiturate-Like Effects.- 5. Summary.- C. Experimental Analysis of Behavioral Effects in Laboratory Animals.- I. Opioids and Opioid Antagonists as Discriminative Stimuli.- 1. Opioid Agonists.- 2. Pentazocine.- 3. Cyclazocine-Like Antagonists.- II. Effects of Opioids and Opioid Antagonists on Schedule-Controlled Behavior.- 1. Effects of Morphine on Schedule-Controlled Behavior.- 2. Tolerance to the Behavioral Effects of Morphine.- 3. Self-Administration of Morphine.- 4. Opioid Antagonists.- 5. Discussion.- D. Summary and Conclusions.- References.- 14 Hypnotics.- A. Hypnotics and Sleep Disorders.- B. Commonly Used Hypnotics.- I. Barbiturates.- II. Chloral Hydrate.- III. Benzodiazepines.- IV. Piperidinediones.- 1. Glutethimide.- 2. Methyprylon.- V. Carbamates.- 1. Ethinamate.- 2. Meprobamate.- VI. Methaqualone.- VII. Ethchlorvynol.- VIII. Paraldehyde.- C. Mode of Action of Hypnotics.- I. Excitatory Processes.- 1. Acetylcholine.- 2. NE.- 3. Serotonin.- 4. Glutamate.- II. Inhibitory Processes.- 1. Postsynaptic Inhibition.- 2. Presynaptic Inhibition.- 3. ?-Aminobutyric Acid (GABA).- III. Release of Neurotransmitters.- IV. Stereoisomers of Barbiturates.- D. Site of Action.- I. Spinal Cord.- II. Brain Stem and Cerebellum.- III. Reticular-Activating System and EEG.- E. Tolerance and Dependence.- I. Tolerance.- 1. Measurement of Tolerance.- 2. Acute Tolerance.- II. Physical Dependence.- 1. Man.- 2. Cat.- 3. Dog.- 4. Monkey.- 5. Rat.- F. Abuse of Sedative Hypnotics.- I. Prescription.- II. Abuse.- G. Conclusions.- References.- 15 Anticholinergics.- A. Introduction.- B. Structure — Activity Relationships.- I. Stereospeciflcity.- II. Non-Esteratic Anticholinergics.- C. Behavioral and Neurologic Effects.- D. Electrophysiologic Effects.- E. Central Cholinergic Pathways and Systems.- F. Sites of Anticholinergic Action in Brain.- I. Competition Between Behavioral Potency and Receptor Affinity.- G. Conformational Analysis of Glycolate Esters.- H. Theoretical Models of Muscarinic Receptor.- I. Multiple Configurational States of the Muscarinic Receptor from Brain.- II. Use of Affinity-Labeled Sepharose for Purification of Muscarinic Receptor from Brain.- I. Possible Role of Calcium in Anticholinergic Action.- J. Clinical Use of Anticholinergics.- References.- 16 Central Nervous Actions of Beta-Adrenoceptor Antagonists.- A. Introduction.- B. Pharmacological Heterogeneity and Access to the Brain of Beta-Adrenoceptor Antagonists.- C. Evidence for Beta-Adrenoceptors in the CNS.- I. Biochemical Evidence.- II. Electrophysiological Evidence.- D. Neuropharmacological and Behavioral Effects of Beta-Adrenoceptor Antagonists.- I. Central Nervous Effects in Animals.- II. Central Nervous Effects in Man.- E. Therapeutic Effects in Psychiatric and Neurological Disorders.- I. Anxiety.- II. Drug Dependence and Abuse.- III. Tremor.- IV. Migraine.- V. Schizophrenia and Other Behavioral Disorders.- F. Summary and Conclusions.- References.- 17 Caffeine.- A. Introduction.- B. Experiments in Humans.- I. Effects on Various Psychological Parameters.- 1. Mood.- 2. Attention, Concentration and Vigilance.- 3. Fatigue and Sleep.- II. Effects on Motor Performance.- 1. Total Work Output.- 2. Tapping.- 3. Hand Steadiness, Motor Skill and Accuracy.- III. Effects on Psychomotor Parameters.- 1. Reaction Time.- 2. Simple Tasks (Cancellations, Calculations, Reading etc.).- 3. Complex Psychomotor Tests (Typewriting, Pursuit Motor Tasks etc.).- 4. Learning, Memory and Other Intellectual Functions.- IV. Habituation, Tolerance and Dependence.- V. Conclusion.- C. Animal Studies.- I. Motor Activity.- II. Response Rates.- III. Learning.- 1. Discrimination.- 2. Avoidance.- IV. Social Behavior.- V. Conclusion.- References.- 18 Research Methodology in Clinical Trials of Psychotropic Drugs.- A. General Principles for the Clinical Investigation of Psychotropic Drugs.- I. Introduction.- II. Methods for the Assessment of Psychiatric Disorders.- III. Factors Influencing the Effect of Psychotropic Substances.- IV. Specificity of Psychotropic Effects.- B. Strategy of Clinical Investigation.- I. Introduction.- II. Phase I.- 1. Pharmacokinetics.- 2. Pharmacodynamics.- III. Phase II.- IV. Phase III.- C. Special Problems.- I. Introduction.- II. Interfering Factors.- III. Criticism of Quantification.- IV. Double-Blind Conditions.- References.- 19 An International Convention on the Control of Psychotropic Substances.- Author Index.