Emerging Targets and Therapeutics in the Treatment of Psychostimulant Abuse

Preface
Contributors
Chapter One: Glial Modulators as Potential Treatments of Psychostimulant Abuse
Abstract

1 Introduction

2 Molecular Biology and Physiology of the Glia

3 In Vivo Evidence that Modulating Glia and Neuroinflammation Provide Pharmacotherapeutic Possibilities for Psychostimulant Abuse

4 Ongoing or Planned Clinical Studies Examining Glial Modulators in the Treatment of Psychostimulant Abuse

5 Conclusion

Conflict of Interest

Chapter Two: The Vesicular Monoamine Transporter-2
Abstract

1 Methamphetamine Addiction

2 Methamphetamine: Mechanism of Action

3 Identification and Classification of Vesicular Monoamine Transporters

4 VMAT2 Function

5 VMAT2 Binding Sites

6 Aberrant VMAT2 Expression and Function

7 Conclusion

Conflict of Interest

Acknowledgments

Chapter Three: Customizing Monoclonal Antibodies for the Treatment of Methamphetamine Abuse
Abstract

1 Introduction

2 METH Mechanisms of Action, Toxicity, and Current Therapies

3 Therapeutic Monoclonal Antibodies to Counteract METH Effects

4 Predicting Therapeutic Effectiveness

5 METH Metabolism and Pharmacokinetics: Choosing the Appropriate Animal Testing Model

6 The Role of Affinity, Binding Capacity, and In Vivo Modifications in mAb Function

7 Hapten Design for Improved Target Specificity and mAb Functionality

8 Relationship Between Hapten Structure and mAb Function: Application to Other Antibody Forms

9 Antibody Form and Duration of Action

10 Conclusion

Conflict of Interest

Acknowledgments

Chapter Four: Monoamine Transporter Inhibitors and Substrates as Treatments for Stimulant Abuse
Abstract

1 Introduction

2 Operant Behavior in Medication Development

3 Monoamine Transporters as Molecular Targets for Medication Development

4 Evaluation of Monoamine Transporter Inhibitors and Substrates on Abuse-Related Effects of Psychostimulants

5 Conclusion

Conflict of Interest

Acknowledgments

Chapter Five: Bupropion and Bupropion Analogs as Treatments for CNS Disorders
Abstract

1 Introduction

2 Metabolism of Bupropion

3 Mechanism of Bupropion Therapeutic Properties

4 Animal Behavioral Studies of Bupropion

5 Clinical Studies with Bupropion

6 Bupropion nAChR Binding Site

7 Bupropion and Hydroxybupropion Analog Clinical Development

8 Conclusion

Conflict of Interest

Acknowledgments

Chapter Six: The Role of Guanfacine as a Therapeutic Agent to Address Stress-Related Pathophysiology in Cocaine-Dependent Individuals
Abstract

1 Introduction

2 Guanfacine as a Medication for Substance Abuse Compared with Other Alpha-2 Adrenergic Agonists

3 Other Potential Anxiolytics and Cognitive Enhancers

4 Long-Term Maintenance of Guanfacine

5 Conclusion

Conflict of Interest

Chapter Seven: Beyond Small-Molecule SAR
Abstract

1 Introduction

2 D3-Selective Drug Design Using Small-Molecule SAR

3 Clinical Studies Targeting the D3 Receptor in the Treatment of Addiction

4 The Structural Basis of D3 over D2 Receptor Selectivity and the Future of Rational Drug Design for D3 Receptor-Selective Ligands

5 Conclusion

Conflict of Interest

Acknowledgments

Chapter Eight: Dopamine D4 Receptors in Psychostimulant Addiction
Abstract

1 Introduction

2 DRD4 and Psychostimulant Addiction

3 Conclusion

Conflict of Interest

Acknowledgments

Chapter Nine: Sigma (σ) Receptors as Potential Therapeutic Targets to Mitigate Psychostimulant Effects
Abstract

1 Introduction

2 Background on σ Receptors

3 Cocaine and σ Receptors

4 Methamphetamine and σ Receptors

5 Clinical Implications

6 Conclusion

Conflict of Interest

Acknowledgments

Chapter Ten: Mixed Kappa/Mu Partial Opioid Agonists as Potential Treatments for Cocaine Dependence
Abstract

1 Introduction

2 Opioids Used to Treat Drug and Alcohol Dependence: Preclinical and Clinical Evidence

3 Mechanistic and In Vitro Characterization of Mixed μ/κ Agonists

4 Conclusion

Conflict of Interest

Acknowledgments

Chapter Eleven: The Combination of Metyrapone and Oxazepam for the Treatment of Cocaine and Other Drug Addictions
Abstract

1 Introduction

2 Stress and Addiction

3 Cocaine and Benzodiazepines

4 Stress and Cocaine Reinforcement

5 Stress and Relapse

6 Rationale for Testing Drug Combinations

7 Our Hypothesis Changes

8 Medial Prefrontal Cortex and Cocaine

9 Neurosteroids and the Combination of Metyrapone and Oxazepam

10 Conclusion

Conflict of Interest

Chapter Twelve: Salvinorin A Analogs and Other Kappa-Opioid Receptor Compounds as Treatments for Cocaine Abuse
Abstract

1 Introduction

2 Kappa-Opioid Receptors and the Endogenous Opioid System

3 Kappa-Opioid Regulation of Dopamine Systems

4 Effects of Drugs of Abuse on the Kappa-Opioid System

5 Effects of Kappa-Opioid Receptor Agonists on Drug Addiction

6 Animal Studies with Sal A

7 Effects of Sal A on Depression

8 Antidepressive Effects of Sal A

9 Prodepressive Effects of Sal A

10 Signaling Pathways Regulated by Sal A

11 Pharmacokinetics of Sal A

12 Sal A Analogs

13 Conclusion

Conflict of Interest

Chapter Thirteen: Nicotinic Receptor Antagonists as Treatments for Nicotine Abuse
Abstract

1 Introduction

2 Current Smoking Cessation Therapies that Target nAChRs

3 Emerging Potential Therapeutics for Treatment of Tobacco Dependence

4 Small-Molecule Surrogates of α-CtxMII as Smoking Cessation Agents

5 Monoquaternary Ammonium Salts Derived from N-Methylnicotinium Ion as Nicotinic Receptor Antagonists

6 Conclusion

Conflict of Interest

Acknowledgments

Chapter Fourteen: New Directions in Nicotine Vaccine Design and Use
Abstract

1 Introduction

2 Status of First-Generation Nicotine Vaccines

3 Limitations of First-Generation Nicotine Vaccines

4 Limitations of Vaccination as a General Strategy for Treating Nicotine Addiction

5 Design of Nicotine Vaccines

6 Strategies for Improving Vaccine Efficacy

7 Alternatives to Vaccination

8 Translational Considerations

9 Conclusion

Conflict of Interest

Acknowledgments

Chapter Fifteen: Bath Salts, Mephedrone, and Methylenedioxypyrovalerone as Emerging Illicit Drugs That Will Need Targeted Therapeutic Intervention
Abstract

1 Introduction

2 PIA Analogs: Nomenclature and Pharmacological Assays

3 Cathinone Analogs: Historical Perspectives

4 Amphetamine (i.e., Phenylisopropylamine) Analogs

5 Synthetic Cathinones: Specific Agents

6 Synthetic Cathinones: Mechanisms of Action and Behavioral Studies

7 Synthetic Cathinones: Human Studies

8 Conclusion

Conflict of Interest

Acknowledgments

Index