

Beschreibung
The volumes on "psychotropic substances" in the Handbook of Experimental Phar macology series clearly show that the classical concept of this discipline has become too narrow in recent years. For instance, what substances are psychotropic is determined not b...The volumes on "psychotropic substances" in the Handbook of Experimental Phar macology series clearly show that the classical concept of this discipline has become too narrow in recent years. For instance, what substances are psychotropic is determined not by the criteria of the animal trial, i.e. by experimental pharmacology, but by their action on the psy che, which in the final analysis is only accessible to us in man. Psychotropic substances force experimental pharmacology (and thus also this Handbook) outside its tradition allimits, which have essentially depended on animal studies. The antipsychotics and antidepressants were not discovered in animal ex periments, but by chance (or more precisely, by clinical empiricism). Experienced psy chiatrists trained in the observation of patients recognised the efficacy of drugs, the beneficial effect of which nobody had dreamed of before: DELAY and DENICKER in the case of chlorpormazine, KLINE in the case of the monoamine oxidase inhibitors and KUHN in the case of imipramine. It was only after these discoveries that the pharma cologists developed experimental models of the psychoses in animal experiments. However, even today we still do not know with certainty which of the effects shown in animals is relevant for the clinical effect despite the vast abundance of individual investigations. For many years, this uncertainty led to the testing of antipsychotics (e.g. of the neuroleptic type) in models which actually produced the undesired effects.
Inhalt
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 …
