Abstract
The mechanisms of lithium action are not known in detail. First messengers, second messengers, and gene expression all appear to be involved: the wide breadth of targets makes the lithium therapeutic path difficult to disentangle. In the present paper, we focused on the most direct biochemical lithium targets at therapeutic concentration, for which some pharmacogenetic finding is present (i.e. inositol mono phosphatase (IMPase), inositol polyphosphate-1-phosphatase (IPPase) and glycogen sinthase kinase 3 beta (GSK-3 beta)). They are all inhibited by lithium at therapeutic concentrations and are representative of the inositol depletion and of the GSK-3 beta based theories of lithium action. Then we surveyed gene variants on those targets that have been associated also with bipolar disorder. On the basis of the molecular characteristics of these proteins, we suggest a set of critical genetic variations. IMPase2, IPPase and GSK-3 beta gene appear to be good candidates for the analysis of lithium prophylactic efficacy and bipolar disorder phenotypes but the genetic association analysis conducted so far reported negative or not unequivocal finding. This may be due to the incomplete coverage of gene mutations in most studies or to the several actions that lithium is thought to perform and trigger in cell machinery, including receptors, calcium equilibrium, gene expression, activation of neuroprotective paths and other yet undetected or less considered mechanisms.
Keywords: Lithium, pharmacogenetics, candidate gene, bipolar disorder, psychopharmacology
Current Medicinal Chemistry
Title: Lithium Pharmacodynamics and Pharmacogenetics: Focus on Inositol Mono Phosphatase (IMPase), Inositol Poliphosphatase (IPPase) and Glycogen Sinthase Kinase 3 Beta (GSK-3 Beta)
Volume: 16 Issue: 15
Author(s): Alessandro Serretti, Antonio Drago and Diana De Ronchi
Affiliation:
Keywords: Lithium, pharmacogenetics, candidate gene, bipolar disorder, psychopharmacology
Abstract: The mechanisms of lithium action are not known in detail. First messengers, second messengers, and gene expression all appear to be involved: the wide breadth of targets makes the lithium therapeutic path difficult to disentangle. In the present paper, we focused on the most direct biochemical lithium targets at therapeutic concentration, for which some pharmacogenetic finding is present (i.e. inositol mono phosphatase (IMPase), inositol polyphosphate-1-phosphatase (IPPase) and glycogen sinthase kinase 3 beta (GSK-3 beta)). They are all inhibited by lithium at therapeutic concentrations and are representative of the inositol depletion and of the GSK-3 beta based theories of lithium action. Then we surveyed gene variants on those targets that have been associated also with bipolar disorder. On the basis of the molecular characteristics of these proteins, we suggest a set of critical genetic variations. IMPase2, IPPase and GSK-3 beta gene appear to be good candidates for the analysis of lithium prophylactic efficacy and bipolar disorder phenotypes but the genetic association analysis conducted so far reported negative or not unequivocal finding. This may be due to the incomplete coverage of gene mutations in most studies or to the several actions that lithium is thought to perform and trigger in cell machinery, including receptors, calcium equilibrium, gene expression, activation of neuroprotective paths and other yet undetected or less considered mechanisms.
Export Options
About this article
Cite this article as:
Serretti Alessandro, Drago Antonio and De Ronchi Diana, Lithium Pharmacodynamics and Pharmacogenetics: Focus on Inositol Mono Phosphatase (IMPase), Inositol Poliphosphatase (IPPase) and Glycogen Sinthase Kinase 3 Beta (GSK-3 Beta), Current Medicinal Chemistry 2009; 16 (15) . https://dx.doi.org/10.2174/092986709788186101
DOI https://dx.doi.org/10.2174/092986709788186101 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Editorial [Hot Topic: Regulation of Brain Functions by Adenosine A2A Receptors:Implication for Therapeutics (Executive Editor: Patrizia Popoli) ]
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Neuropharmacology From Substance Dependence to Addiction: Impact of a Conceptual Shift on Therapeutic Approaches?
Current Pharmaceutical Design Equol is Neuroprotective During Focal Cerebral Ischemia and Reperfusion that Involves p-Src and gp91<sup>phox</sup>
Current Neurovascular Research Meet Our Associate Editor
Central Nervous System Agents in Medicinal Chemistry Metabolism-based Drug-drug Interactions in Patients with Chronic Respiratory Diseases: A Review Focusing on Drugs Affecting the Respiratory System
Current Drug Metabolism AMPK as a Potential Anticancer Target - Friend or Foe?
Current Pharmaceutical Design Evaluation of Novel Substituted Furopyridines as Inhibitors of Protein Kinases Related to Tau Pathology in Alzheimer´s Disease
Medicinal Chemistry Using Functional Neuroimaging to Investigate the Mechanisms of Action of Selective Serotonin Reuptake Inhibitors (SSRIs)
Current Pharmaceutical Design Understanding the Molecular Mechanisms of Rifaximin in the Treatment of Gastrointestinal Disorders – A Focus on the Modulation of Host Tissue Function
Mini-Reviews in Medicinal Chemistry The Many Faces of MTA3 Protein in Normal Development and Cancers
Current Protein & Peptide Science Obesity: Genetics, Behavior or a Combination of Both
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Resolvins: Endogenously-Generated Potent Painkilling Substances and their Therapeutic Perspectives
Current Neuropharmacology Perspectives in Medicinal Chemistry: Focusing on the Link between Diabetes, Alzheimer's Disease and Cancer for the Discovery of New Medicines
Current Topics in Medicinal Chemistry Polymeric Materials and Formulation Technologies for Modified-Release Tablet Development
Mini-Reviews in Medicinal Chemistry Invasive and Non-Invasive Electrical Neuromodulation in Trigeminal Nerve Neuralgia: A Systematic Review and Meta-Analysis
Current Neuropharmacology n-3 Polyunsaturated Fatty Acids as Signal Transduction Modulators and Therapeutical Agents in Cancer
Current Signal Transduction Therapy Metformin Eased Cognitive Impairment Induced by Chronic L-methionine Administration: Potential Role of Oxidative Stress
Current Neuropharmacology Tachykinins and their Receptors in Human Malignancies
Current Drug Targets Transcriptional Regulation of Cytochrome P450 Genes by the Nuclear Receptor Hepatocyte Nuclear Factor 4-Alpha
Current Drug Metabolism