Mechanisms of Action
Lithium, the treatment of choice for mania since its usefulness was first reported, has been shown to have varied effects on multiple biological systems, including electrolyte flux and neurochemistry. Recent advances in cellular and molecular biology promise to provide clinicians with a better understanding of the etiology of bipolar disorder and new options for treatment.
Bipolar Medications: Mechanisms of Action presents the treatment and prophylaxis of bipolar disorder. More than 40 investigators share research and insight into the neurobiological mechanisms that help to explain the powerful effects of new antibipolar drugs. This comprehensive text
- Examines valproic acid, lamotrigine, inositol monophosphatase inhibitors, and protein kinase C inhibitors that have the potential to revolutionize clinical practice and provide new hypotheses on the etiology of bipolar disorder
- Presents the current understanding of the cellular mechanisms of action of mood-stabilizing agents
- Discusses the emergence of valproate as a powerful lithium alternative and examines the preliminary indications that lamotrigine will be an effective option
- Examines the issue of withdrawal rebound, which can make lithium ineffective or even counterproductive, and reviews inositol monophosphatase inhibitors that mimic lithium action in patients
- Compares lithium, carbamazepine, and valproate and their differential mechanisms, which could form the basis of a rational polypharmacy of manic depressive illness
- Examines behavioral models important in the screening of new antibipolar compounds and the effects of antibipolar compounds on immediate early genes
Complete with extensive references, tables, and figures, this text is essential reading for any clinician who treats patients with bipolar disorder. It thoroughly documents the latest in psychopharmacology, as well as projecting future advances in the treatment of bipolar disorder.
- Chapter 1. LITHIUM, PHOSPHATIDYLINOSITOL SIGNALING, AND BIPOLAR DISORDER: THE ROLE OF INOSITOL MONOPHOSPHATASE
- Chapter 2. HUMAN EVIDENCE OF THE ROLE OF INOSITOL IN BIPOLAR DISORDER AND ANTIBIPOLAR TREATMENT
- Chapter 3. THE BRAIN POLYAMINE–STRESS RESPONSE: DEVELOPMENT, RECURRENCE AFTER REPETITIVE STRESSOR, AND INHIBITION BY LITHIUM
- Chapter 4. ACUTE INHIBITION BUT CHRONIC UPREGULATION AND STABILIZATION OF GLUTAMATE UPTAKE IN SYNAPTOSOMES BY LITHIUM
- Chapter 5. EFFECTS OF ANTIDEPRESSANT TREATMENTS ON THE G PROTEIN–ADENYLYL CYCLASE AXIS AS THE POSSIBLE BASIS OF THERAPEUTIC ACTION
- Chapter 6. EFFECTS OF LITHIUM AND OTHER MOOD-STABILIZING AGENTS ON THE CYCLIC ADENOSINE MONOPHOSPHATE SIGNALING SYSTEM IN THE BRAIN
- Chapter 7. REGULATION OF SIGNAL TRANSDUCTION PATHWAYS BY MOOD-STABILIZING AGENTS: IMPLICATIONS FOR THE PATHOPHYSIOLOGY AND TREATMENT OF BIPOLAR DISORDER
- Chapter 8. MODULATION OF NEURONAL SIGNAL TRANSDUCTION SYSTEMS BY LITHIUM
- Chapter 9. A MOLECULAR TARGET FOR THE LONG-TERM ACTION OF LITHIUM IN THE BRAIN: A PHOSPHOPROTEIN SUBSTRATE OF PROTEIN KINASE C
- Chapter 10. LITHIUM, CARBAMAZEPINE, AND VALPROATE IN AFFECTIVE ILLNESS: BIOCHEMICAL AND NEUROBIOLOGICAL MECHANISMS
- Chapter 11. POTENTIATION OF IMMEDIATE-EARLY GENE C-FOS EXPRESSION IN CEREBRAL CORTEX BY CHRONIC LITHIUM TREATMENT AFTER 5-HT2A RECEPTOR ACTIVATION
- Chapter 12. BEHAVIORAL CORRELATES OF THE EFFECTS OF LITHIUM ON SECOND-MESSENGER SYSTEMS
- Chapter 13. GUANINE NUCLEOTIDE BINDING PROTEIN DISTURBANCES IN BIPOLAR DISORDER
- Chapter 14. CARBAMAZEPINE AND ADENOSINE RECEPTORS
- Chapter 15. CLINICAL AND BIOLOGICAL INVESTIGATION OF MANIA FOLLOWING LITHIUM WITHDRAWAL
- Chapter 16. VALPROATE IN MANIA
- Chapter 17. EFFICACY OF LAMOTRIGINE IN BIPOLAR DISORDER: PRELIMINARY DATA
- Chapter 18. ATYPICAL ANTIPSYCHOTIC AGENTS IN MANIA: CLINICAL STUDIES
- Chapter 19. CALCIUM CHANNEL BLOCKER
About the Authors
Husseini K. Manji, M.D., F.R.C.P.C., is Director of the Laboratory of Molecular Pathophysiology in the Department of Psychiatry and Behavioral Neurosciences at Wayne State University School of Medicine in Detroit, Michigan.
Charles L. Bowden, M.D., is the Nancy U. Karren Professor and Interim Chair of the Department of Psychiatry at the University of Texas Health Science Center at San Antonio, In San Antonio, Texas.
Robert H. Belmaker, M.D., is Hoffer-Vickar Professor of Psychiatry at Beer Sheva Mental Health Center and on the Faculty of Health Sciences at the Ben Gurion University of the Negev in Beersheva, Israel.
As we approach the end of this century, it is appropriae to consider and celebrate the enormous advances that have been achieved in the reatment of serious brain disorders currently (and misleadingly) termed 'psychiatric' or 'mental.' The major advances have been pharmacological and of these, litium is perhaps the most important as it demonstrated for the first time the validity of this therapeutic approach. While the psychopharmacological revolution that has taken place since Cade first demonstrated the potential efficacy of lithium in the treatment of bipolor illness has been breathtaking, it is ironic that some 50 years later there is still no clear understanding of how this cation produces its therapeutic effects. Mechanisms of Action of Bipolar Treatments is an excellent volume in part because it covers thoroughly the variety of hypothesis that are still under active consideration. Today most of these are focussed on signal transduction systems, the subject of intense current interest in molecular and cell biology. Indeed, as more of these systems and their components become elucidated, it is safe to assume that some will represent yet additional candidate mediators of lithium's therapeutic effects. Another attractive feature of this voulme is that it provides a relatively up-to-date overview of more recently discovered agents that can be useful in the treatment of bipolar illness, including carbamazepine, valproate, lamotrigine, and atypical antipsychotic agents. This volume can be recommended strongly to researchers and practicing clinicians alike as it contains important information that is highly relevant to both.—H. Christian Fibiger, Ph.D., Eli Lilly and Company, Indianapolis, Indiana
The book represents an undertaking of massive scholarship covering a truly extraordinary range of scientific research on the basic and some of the clinical pharmacology of agents used or proposed for use in the treatment of bipolar manic-depressive disorders. The book is a monumental achievement. It is especially impressive in that the field of bipolar disorder therapeutics has made relatively little progress at the theoretical level for many years. Now that a number of promising newer alternatives to lithium are emerging, they can be compared to lithium and its very complex neuropharmacology. This comparative approach is promising to shed light on potential common mechanisms of action of this complex class of drugs. Moreover, the application of newer methods of molecular analysis of signaling, second-messenger, and other cytoregulatory systems shows promise of hypothesis that may produce fresh leads to rationally predicted innovations in therapeutics in this important field.—Ross J. Baldessarini, M.D., Professor of Psychiatry (Neuroscience), Harvard Medical School, Belmont, Massachusetts
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