Drugs for the Treatment of Parkinson's Disease

ISBN-13: 9783642739019 / Angielski / Miękka / 2011 / 599 str.

Donald B. Calne

Opis

This volume provides a comprehensive reference on drugs employed to treat Parkinson's disease. Since pharmacology is dependent upon physiology, and physiology upon anatomy, the multiauthored contents build up from all these disciplines to applied therapeutics. Our knowledge of synaptic mechanisms in the striatum is reviewed; and drugs are considered as therapeutic tools to manipulate synaptic function. Methods of evaluating treatment in Parkinson's disease are discussed in order to provide a background against which the reader can determine whether therapeutic studies are meaningful. The volume deals with old drugs (anticholinergic agents), conventional drugs (levodopa and decarboxylase inhibitors) and new drugs (dopamine agonists). Drugs designed to modify the natural history of Parkinson's disease (antioxidants) are reviewed, and drugs employed to reduce adverse reactions are discussed (extracerebral D2 antagonists). Novel routes for administering drugs are included (parenteral infusions) and finally, current approaches to transplanting dopaminergic cells into the striatum are summarized. This book is intended to meet the needs of physicians who treat Parkinson's disease, to assist pharmacologists who are concerned with the development of improved methods for controlling symptoms, and to stimulate those neurobiologists who have an interest in attempting to slow down the inexorable progress of the disorder.

Spis treści

1 Neurophysiology of Basal Ganglia.- A. Introduction.- B. Electrophysiology of Connections.- I. Peripheral and Cerebral Input to Basal Ganglia.- 1. Striatum.- a. Peripheral Input..- b. Cerebral Input.- 2. Nucleus Subthalamicus.- 3. Substantia Nigra.- II. Internal Basal Ganglia Connections.- 1. Nigrostriatal Dopamine System.- a. Substantia Nigra.- b. Striatum.- 2. Striatopallidal..- 3. Striatonigral.- 4. Nucleus Subthalamicus.- 5. Nucleus Tegmenti Pedunculopontinus.- III. Output of Basal Ganglia.- 1. Pallidothalamic.- 2. Nigrothalamic.- 3. Pallidohabenular.- 4. Nigrocollicular.- 5. Nucleus Tegmenti Pedunculopontinus.- C. Motor Control Functions.- I. Anatomic Considerations.- II. Lesions, Cooling, and Local Drug Injections.- 1. Striatum.- 2. Globus Pallidus.- 3. Substantia Nigra Pars Reticulata.- 4. Nucleus Subthalamicus.- III. Neuronal Recordings.- 1. Striatum.- 2. Globus Pallidus.- 3. Substantia Nigra Pars Reticulata.- 4. Nucleus Subthalamicus.- D. Higher Functions.- I. Anatomy of Connections.- 1. Cortical Input.- 2. Limbic Input.- 3. Output.- II. Neuropsychologic Deficits After Lesions.- III. Neuronal Recordings.- 1. Untrained Behavior.- 2. Context-Dependent Responses to Directly Triggering Stimuli.- 3. Preparation to Act.- a. Nondiscriminative Instructions.- b. Discriminative Instructions.- c. Delayed Response Tasks.- d. Self-Initiated Acts.- E. Dopaminergic Functions.- I. Animal Models of Parkinsonism.- 1. Monkey.- 2. Rodent.- II. Impulse activity of Dopamine Neurons.- 1. Peripheral Input Under Anesthesia.- 2. Relations to Behavior.- a. Execution of Movements.- b. Responses to Stimuli.- c. Preparation to Act.- 3. Comparison with Deficits.- F. Conclusions.- I. Functional Connectivity.- 1. Lateralization of Function.- 2. Disinhibition of Target Structures.- 3. The “Extrapyramidal Motor System”.- II. Dopamine System.- 1. Mismatch Between Negative and Positive Image.- 2. Paradoxical Kinesia.- 3. Neuronal Activity in Target Areas of DA Neurons.- III. Corticostriatal Activity.- References.- 2 Pathology of Parkinson’s Syndrome.- A. Introduction.- B. Cytoskeletal Pathology.- I. Lewy Bodies.- II. Hirano Bodies.- III. Intracytoplasmic Eosinophilic Granules.- IV. Marinesco Bodies.- V. Neurofibrillary Tangles.- 1. Alzheimer’s Neurofibrillary Tangles.- 2. Tangles in Progressive Supranuclear Palsy.- VI. Granulovacuolar Degeneration.- VII. Axonal Dystrophy and Grumelous Degeneration.- VIII. Neuritic Plaques and Amyloid.- C. Major Types of Parkinsonism.- I. Parkinson’s Disease.- II. Parkinson’s Disease and Alzheimer’s Disease.- III. Diffuse Lewy Body Disease.- IV. Multisystem Degenerations.- V. Parkinson-Dementia Complex.- VI. Progressive Supranuclear Palsy.- VII. Postencephalitic Parkinsonism.- VIII. Vascular or Multi-infarct Parkinsonism.- IX. Toxic Parkinsonism.- X. Symptomatic Parkinsonism.- D. Morphological Correlates of Pathobiochemistry.- I. Dopaminergic System.- 1. Substantia Nigra and Ventral Tegmental Area.- 2. Striatopallidum and Other CNS Areas.- II. Noradrenergic System.- 1. Locus Ceruleus.- 2. Dorsal Vagal Nucleus.- III. Serotonergic System.- IV. Cholinergic Systems.- 1. Nucleus Basalis of Meynert.- 2. Nucleus Tegmenti Pedunculopantinus.- 3. Westphal-Edinger Nucleus.- V. Peptidergic Systems.- E. Morphological Effects of Levodopa Treatment.- F. Pathology of Dementia in Parkinson’s Disease.- G. Concluding Remarks.- References.- 3 Biochemical Neuroanatomy of the Basal Ganglia.- A. Introduction.- B. Neurotransmitters in the Extrapyramidal System.- I. Type I: Amino Acid Neurotransmitters.- II. Type II: Amine Neurotransmitters.- III. Type III: Peptide Neurotransmitters.- IV. Receptor Subtypes.- C. Heterogeneities in Extrapyramidal Nuclei.- I. Mosaics or Gradients.- II. Differences Between Caudate, Putamen, and Nucleus Accumbens.- D. Interconnections in the Extrapyramidal System.- E. Some Hypotheses as to the Role of Various Tracts in the Extrapyramidal System.- F. Conclusions.- G. Appendix: Afferents and Efferents of Extrapyramidal Nuclei.- References.- 4 Receptors in the Basal Ganglia.- A. Introduction.- B. Neurotransmitter Receptor Properties.- C. Dopamine Receptors.- I. Properties and Subtypes.- II. Distribution.- III. Dopamine Receptors in Parkinson’s Disease.- IV. In Vivo Studies.- D. GABA Receptors.- E. Acetylcholine Receptors.- F. Opiate Receptors..- G. Other Receptors.- H. Summary.- References.- 5 Imaging the Basal Ganglia.- A. Introduction.- B. Structural Imaging Techniques.- I. Methodology.- 1. X-Ray Computed Tomography (CT).- 2. Magnetic Resonance Imaging (MRI).- II. Parkinson’s Disease.- III. Huntington’s Disease.- IV. Dystonia.- V. Other Movement Disorders.- C. Functional Imaging Techniques.- I. Methodology.- 1. Positron Emission Tomography (PET).- a. Cerebral Blood Flow and Metabolism.- b. Presynaptic Dopaminergic Function.- c. Dopamine Receptors.- 2. Single-Photon Emission Computed Tomography (SPECT)..- II. Parkinson’s Disease..- III. Huntington’s Disease.- IV. Dystonia.- D. Conclusions..- References.- 6 The Neurochemical Basis of the Pharmacology of Parkinson’s Disease.- A. Introduction.- B. The Basic Neurochemical Pathology of Parkinson’s Disease.- I. The Nigrostriatal Dopamine Neuron System.- II. Extrastriatal Dopamine Neurons.- III. Nondopamine Neuron Systems.- C. Pathophysiologic and Pharmacologic Significance of the Biochemical Brain Abnormalities in Parkinson’s Disease.- I. Nigrostriatal Dopamine Loss.- II. Extrastriatal Dopamine Changes.- III. Nondopamine Changes.- 1. Changes in the Basal Ganglia.- a. Norepinephrine.- b. Acetylcholine.- c. ?-Aminobutyric Acid.- d. Serotonin, Neuropeptides.- 2. Changes Outside the Basal Ganglia.- D. Striatal Dopamine Deficiency and the Pharmacotherapy of Parkinson’s Disease: Special Aspects of Dopamine Substitution.- I. Compensatory Changes in the Nigrostriatal Dopamine Neurons.- II. Compensated and Decompensated Stages of Parkinson’s Disease and the Goal of Dopamine Substitution.- III. The Role of the Compensatory Changes for Dopamine Substitution.- 1. The Role of Presynaptic Overactivity.- 2. The Importance of Postsynaptic Supersensitivity for the Pharmacology of Parkinson’s Disease.- a. Special Sensitivity of the Parkinsonian Striatum to Dopamine Substitution.- b. Regional Selectivity of Dopamine Substitution Therapy..- c. New approaches to Dopamine Substitution.- ?. Selective Dopamine Autoreceptor Agonists as a New Class of Specific Potential Antiparkinsonian Agents.- ß. Autografting of Dopamine-Producing Cells into the Parkinsonian Striatum.- E. Prospects of Preventive Drug Treatment in Parkinson’s Disease.- References.- 7 Pyridine Toxins.- A. Introduction.- B. What are Pyridines?.- I. Historical Background.- II. Structure and Chemistry.- III. Biologic Role.- IV. Distribution of Pyridines.- C. Pyridines as Toxins.- I. History.- II. Animal Models.- 1. Invertebrates.- 2. Amphibia.- 3. Rodents.- 4. Cat.- 5. Dog.- 6. Primates.- D. Factors Affecting Toxicity.- I. Mechanism of Action.- II. Toxicokinetic and Toxicodynamic Effects.- III. Species Differences.- IV. Neuromelanin..- V. Age Differences.- E. Pyridines as Protectors?.- F. Toxic Tetrahydropyridines: A Growing Family.- G. Pyridines and Parkinson’s Disease.- References.- 8 The Relationship Between Parkinson’s Disease and Other Movement Disorders.- A. Introduction.- B. Secondary Parkinsonism.- I. Drug-Induced Parkinsonism.- II. Toxin-Induced Parkinsonism.- 1. Manganese.- 2. Carbon Monoxide.- 3. Cyanide.- 4. Carbon Disulfide.- 5. Other Toxins.- III. Metabolic Causes of Parkinsonism.- 1. Hypoparathyroidism.- 2. Acquired Hepatocerebral Degeneration.- 3. Other Metabolic Causes.- IV. Postencephalitic Parkinsonism and Slow Virus Infections.- V. Vascular Parkinsonism.- VI. Brain Tumors.- VII. Trauma.- VIII. Hydrocephalus.- IX. Syringomesencephalia.- C. Sporadic Multiple System Degenerations (Parkinsonism-Plus).- I. Progressive Supranuclear Palsy.- II. Shy-Drager Syndrome.- III. Olivopontocerebellar Atrophies.- IV. Corticobasal Degeneration.- V. Parkinsonism-Dementia-ALS Complex.- VI. Striatonigral Degeneration.- D. Inherited Multiple System Degenerations.- I. Huntington’s Disease.- II. Wilson’s Disease.- III. Hallervorden-Spatz Disease.- IV. Other Familial Parkinsonian Syndromes.- V. Familial Basal Ganglia Calcifications.- VI. Neuroacanthocytosis.- References.- 9 Evaluation of Parkinson’s Disease.- A. Introduction.- B. Subjective Assessment.- C. Objective Assessment.- I. Tremor.- II. Rigidity.- III. Hypokinesia.- D. Summary.- References.- 10 Clinical Trials for Parkinson’s Disease.- A. Introduction.- B. Phases.- C. Design.- D. Recruitment.- E. Assessment.- F. Statistical Analysis.- G. Conclusions.- References.- 11 Experimental Therapeutics Directed at the Pathogenesis of Parkinson’s Disease.- A. Introduction.- B. General Strategies for Prevention and Protection.- C. Antioxidative Pharmacotherapies.- D. Clinical Trial of Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP).- I. Pilot Studies and Candidate Drugs.- II. Factorial Design.- III. Major Response Variable.- IV. Sample Size Estimates.- V. Symptomatic or Protective Effects?.- VI. Recruitment.- VII. Potential Pitfalls.- E. Animal Models.- F. Neural Grafting.- G. Summary.- References.- 12 Anticholinergic Drugs and Amantadine in the Treatment of Parkinson’s Disease.- A. Introduction.- B. Anticholinergics.- I. Introduction.- II. Mechanism of Action.- III. Pharmacokinetics.- IV. Clinical Effects.- V. Side Effects.- VI. Conclusions.- C. Amantadine.- I. Introduction.- II. Mechanism of Action.- III. Pharmacokinetics.- IV. Clinical Effects.- V. Side Effects.- VI. Conclusions.- References.- 13 The Pharmacology of Levodopa in Treatment of Parkinson’s Disease: An Update.- A. Introduction.- B. The Efficacy of Levodopa in Parkinsonism.- I. Background.- II. Clinical Effectiveness of Levodopa in Parkinson’s Disease.- III. Use of Levodopa in Other Forms of Parkinsonism and Other Movement Disorders.- IV. Therapeutic Principles for Levodopa.- C. Clinical Aspects of Levodopa Pharmacokinetics, Pharmacodynamics, and Metabolism.- I. Levodopa Pharmacokinetics.- II. Levodopa Metabolism: 3-O-Methyldopa and Other Metabolites.- III. Other Metabolic Effects of Levodopa.- D. Other Effects of Levodopa.- E. Pharmacodynamics of Levodopa Therapy.- F. Mechanism of Action of Levodopa in Parkinsonism.- G. Levodopa Preparations.- I. Decarboxylase Inhibitors.- II. Sustained-Release Forms.- III. Enhanced Delivery and Uptake.- H. Therapeutic Uses for Levodopa Other Than Parkinsonism.- J. Clinical Issues Regarding Initiation of Levodopa Therapy.- I. “Early” Versus “Delayed” Use of Levodopa.- II. “Low Dose” Levodopa Regimens.- K. Clinical Issues Regarding “Drug Holiday”.- References.- 14 Adverse Effects of Levodopa in Parkinson’s Disease.- A. Historical Aspects of Adverse Effects.- B. Classification, Pathophysiology, and Treatment of Adverse Effects.- I. Peripheral Adverse Effects.- 1. Gastrointestinal Symptoms.- 2. Cardiac Dysrhythmias.- 3. Melanoma.- II. Central Adverse Effects.- 1. Dyskinesias.- a. Chorea.- ?. Peak-Dose Chorea.- ß. Diphasic Chorea.- b. Dystonia.- ?. Peak-Dose Dystonia.- ß. Diphasic Dystonia.- ?. “Off” Dystonia.- c. Myoclonus.- d. Simultaneous Dyskinesias with Parkinsonism.- 2. Tachykinesia with Hypokinesia.- a. Tachyphemia.- b. Running Gait.- 3. Fluctuations.- a. “Wearing-Off”.- b. “Sudden Off”.- c. “Random Off”.- d. Yo-yo-ing.- e. Episodic Failure to Respond to Each Dose.- f. “Delayed On”.- g. Weak Levodopa Response at End of Day.- h. Response Varies in Relation to Meals.- 4. “Freezing”.- 5. Mental Changes.- 6. Loss of Efficacy.- a. Caused by Pyridoxine.- b. With Continuing Treatment.- 7. Miscellaneous.- a. Altered Sleep-Wake Cycle.- b. Hypersexuality.- c. Akathisia.- d. Sweating.- e. Postural Hypotension.- f. Respiratory Distress.- g. Falling.- h. Pain.- j. Increased Parkinsonism.- k. “Neuroleptic Malignant Syndrome”.- References.- 15 Monoamine Oxidase Inhibitors in Parkinson’s Disease.- A. Introduction.- B. The Inhibition of Dopamine Oxidation by (?)-Deprenyl.- C. Cellular Localisation of MAO in the Brain.- D. Safety of (?)-Deprenyl.- E. Assessment of MAO Inhibition In Vivo.- F. Distribution of (?)-Deprenyl in Brain and Body.- G. Metabolism of (?)-Deprenyl to Amphetamine.- H. Other Actions of (?)-Deprenyl.- J. MAO and MPTP.- K. Postscript.- References.- 16 Clinical Actions of l-Deprenyl in Parkinson’s Disease.- A. Introduction.- B. Pharmacology.- C. Clinical Trials.- I. Combined Use of Deprenyl with Levodopa.- II. L-Deprenyl as Monotherapy..- D. Summary.- References.- 17 Update on Bromocriptine in Parkinson’s Disease.- A. Introduction.- B. Side Effects of Levodopa.- C. Mechanisms for Decline in Response.- D. Treatment of Response Fluctuations: Bromocriptine.- E. Studies of Bromocriptine Therapy.- F. Pharmacology of Bromocriptine.- References.- 18 Pergolide in the Treatment of Parkinson’s Disease.- A. Chemistry and Pharmacology.- B. Clinical Studies.- I. Open-Label Studies.- II. Double-Blind Studies.- III. A Long-term Follow-up Study.- C. How to Administer.- D. Side Effects.- References.- 19 Lisuride Pharmacology and Treatment of Parkinson’s Disease.- A. Chemistry.- B. Toxicology.- C. Pharmacokinetics.- D. Biochemistry and Pharmacology.- I. Receptor Binding.- II. Biochemistry.- III. Pharmacology.- IV. Neurophysiology.- E. Clinical Applications.- I. Clinical Pharmacology.- II. Applications in Clinical Endocrinology.- F. Lisuride in Neurological Diseases.- I. Parkinson’s Disease and Related Disorders.- 1. Oral Application.- 2. Parenteral Application.- 3. Subcutaneous Lisuride: Continuous Dopaminergic Stimulation.- II. Other Motor Disturbances.- III. Migraine.- G. Conclusion.- References.- 20 Domperidone and Parkinson’s Disease.- A. Introduction.- B. Domperidone.- I. Animal Pharmacology.- II. Pharmacokinetics in Humans.- III. Behavioural Effects.- IV. Effect on the Pharmacokinetic Behaviour of Levodopa.- C. Effect of Domperidone on Levodopa Response.- I. Therapeutic Response to Levodopa in Parkinsonism.- II. Dopamine Agonist-Induced Sickness.- III. Levodopa-Associated Cardiovascular Problems.- 1. Domperidone-and Levodopa-Induced Hypotension.- 2. Domperidone and Cardiac Dysrhythmias.- 3. Domperidone and Cerebral Blood Flow.- IV. Levodopa-Associated Respiratory Problems.- D. Comparison of Domperidone with Metoclopramide and Other Neuroleptics in the Management of Parkinson’s Disease.- E. Comparison of Domperidone with Decarboxylase Inhibitors in the Management of Parkinson’s Disease.- References.- 21 New Routes of Administration for Antiparkinsonian Therapy.- A. Introduction.- B. Delivery Methods.- I. Enteral Administration.- II. Intravenous Administration.- III. Subcutaneous Administration.- IV. Transcutaneous Administration.- C. Clinical Studies.- I. Enteral Routes.- II. Intravenous Administration.- 1. Levodopa.- 2. Lisuride.- 3. Apomorphine.- III. Subcutaneous Infusions.- IV. Transdermal Application.- D. Conclusion.- References.- 22 Treatment of Parkinsonian Features in Neurological Disorders Other than Parkinson’s Disease.- A. Introduction.- B. Drug-Induced Parkinsonism.- C. Wilson’s Disease.- D. Multiple System Degenerations.- I. Striatonigral Degeneration.- II. Olivopontocerebellar Atrophy.- III. Shy-Drager Syndrome.- IV. Progressive Supranuclear Palsy.- V. Senile Parkinsonism.- VI. The ALS-Parkinson-Dementia Complex of Guam.- VII. Joseph Disease.- E. Other Types of Parkinsonism.- I. Postencephalitic Parkinsonism.- II. Parkinsonism Due to Toxins.- III. Hypoparathyroidism.- IV. Huntington’s Disease.- F. Conclusions.- References.- 23 Management of Psychiatric Symptoms in Parkinson’s Disease.- A. Introduction.- B. Depression.- C. Psychosis and Related Disorders.- I. Early Onset Psychosis.- II. Late Onset Psychosis.- D. Drug-Induced Hallucinatory Syndromes.- I. Anticholinergic Delirium.- II. Hallucinations with a Clear Sensorium.- E. Treatment of Psychosis.- F. Aberrant Sexual Behavior.- References.- 24 Intracranial grafts for the treatment of Parkinson’s Disease.- A. Introduction.- B. Sources of Dopamine-Secreting Cells.- C. Neural and Adrenal Grafts in Animal Models of Parkinson’s Disease.- I. Studies in the Rat.- II. Studies in Primates.- D. Dopaminergic Grafts in Humans.- E. Conclusions.- References.