Monoamine Oxidases and their Inhibitors

CONTRIBUTORS

PREFACE

STRUCTURAL PROPERTIES OF HUMAN MONOAMINE OXIDASES A AND B

I. Introduction

II. Crystallization of Purified MAO-B and MAO-A

III. Structure of Human MAO-B

IV. Structure of Human MAO-A and Comparison with Rat MAO-A

V. Insights into Membrane Binding of MAO-A and MAO-B

VI. Structural Basis for Inhibitor-Binding Specificities of MAO-A and MAO-B

VII. Conclusions and Future Prospects

BEHAVIORAL OUTCOMES OF MONOAMINE OXIDASE DEFICIENCY: PRECLINICAL AND CLINICAL EVIDENCE

I. General Characteristics of Monoamine Oxidase

II. Phenotypical Outcomes of MAO-A Deficit

III. Phenotypical Outcomes of MAO-B Deficit

IV. Phenotypical Outcomes of Combined MAO-A and MAO-B Deficit

V. Conclusions

KINETIC BEHAVIOR AND REVERSIBLE INHIBITION OF MONOAMINE OXIDASES—ENZYMES THAT MANY WANT DEAD

I. Introduction

II. Some Basics of Enzyme Inhibition

III. Systems Behavior of Reversible Inhibitors

IV. How Can Kinetic Studies of MAO Help?

V. Tight-Binding Inhibitors

VI. Recovery from Inhibition

VII. Conclusions

THE PHARMACOLOGY OF SELEGILINE

I. Historical Aspects of Selegiline

II. The Multiplicity of Monoamine Oxidase

III. The Pharmacology of MAO-B Inhibition

IV. Structure–Activity Relationship Studies

V. Effects of Selegiline Not Relating to MAO-B Inhibition

VI. Antiapoptotic Effect of Selegiline

VII. Pharmacokinetics of Selegiline

VIII. Metabolism of Selegiline

IX. The Role of Birkmayer and His Group in the Introduction of Selegiline in the Therapy of Parkinson’s Disease

X. Future Perspectives

XI. Overall Conclusions

TYPE A MONOAMINE OXIDASE REGULATES LIFE AND DEATH OF NEURONS IN NEURODEGENERATION AND NEUROPROTECTION

I. Introduction

II. Type A and B MAO in Cell Death of Neurons

III. MAO-A in Neuroprotection by MAO-Is

IV. MAO-A in Induction of Neurotrophic Factors by MAO-Is

V. Is MAO-A the Binding Site of MAO-Is for Induction of Neuroprotective Genes?

VI. Signal Pathway for Induction of Prosurvival Genes by MAO-Is

VII. Discussion

MULTIMODAL DRUGS AND THEIR FUTURE FOR ALZHEIMER’S AND PARKINSON’S DISEASE

I. Introduction

II. Concepts in Multimodal Drug Design

III. Monoamine Oxidase as a Common Target in AD and PD

IV. Multimodal Drugs That Target MAO (1)

V. Multimodal Drugs That Target MAO (2)

VI. Multimodal Drugs That Target MAO (3)

VII. Multimodal Drugs That Target Memory and Neurogenesis

VIII. Conclusion

NEUROPROTECTIVE PROFILE OF THE MULTITARGET DRUG RASAGILINE IN PARKINSON’S DISEASE

I. Introduction

II. Multiple Activities of Rasagiline

III. The Major Metabolite of Rasagiline, 1-(R)-Aminoindan

IV. Summary and Conclusions

RASAGILINE IN PARKINSON’S DISEASE

I. Introduction

II. In Vivo and In Vitro Neuroprotective Effects of Rasagiline

III. Pharmacokinetics and Pharmacodynamics

IV. Evidence for the Symptomatic Benefits of Rasagiline in PD

V. Evidence for Disease Modification with Rasagiline in PD

VI. Adverse Effects

VII. Conclusion

SELECTIVE INHIBITORS OF MONOAMINE OXIDASE TYPE B AND THE “CHEESE EFFECT”

I. Introduction

II. Pharmacology of Tyramine

III. Mechanism of “Cheese Effect”

IV. Cardiovascular Actions of Tyramine

V. Selegiline

VI. Clinical Use of Selegiline and Cheese Effect

VII. Clinical Use of Rasagiline and Cheese Effect

VIII. Reversible Inhibitors of MAO-B

IX. Modification of L-Dopa Cardiovascular Response by Selective Inhibitors of MAO-B

X. Tyramine Content in Foods

XI. Treatment of Cheese Reaction

XII. Specific Foods

XIII. Fish Sauces

XIV. Meat

XV. Beer and Wine

XVI. Conclusions

A NOVEL ANTI-ALZHEIMER’S DISEASE DRUG, LADOSTIGIL

I. Introduction

II. The Underlying Strategy in the Design of Ladostigil

III. MAO Inhibition and Antidepressant Activity of Ladostigil

IV. ChE Inhibitory Activity of Ladostigil

V. Neuroprotective Activities of Ladostigil in Preclinical Models of Neurodegeneration

VI. Mechanism of Action of Ladostigil

VII. Summary and Future Perspectives

NOVEL MAO-B INHIBITORS

I. Introduction

II. MAO-B Inhibitors

III. Apoptosis in PD

IV. Clinical Potential of PF9601N

V. Concluding Remarks

Subject Index

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