Abstract
Modafinil, (RS)-2-(diphenylmethylsulfinyl)acetamide derivative (Modiodal, Provigil), is a vigilance-promoting agent which reduces sleep episodes by improving wakefulness. It is approved by the USA FDA for narcolepsy, shiftwork sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure. Unlike classical psychostimulants such as amphetamine and amphetamine-like compounds, the awaking effect of modafinil is not associated with a disturbance of nighttime sleep, tolerance, and sensitization. Its precise mechanism of action is still unclear. In animal studies, modafinil and its analogues have been shown to modify dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic pathways. Besides the approved use in sleep disorders, modafinil has been investigated for the treatment of fatigue, impaired cognition and some symptoms in a number of other disorders. In particular, clinical studies seem to indicate that the drug could be particularly successful in the treatment of depression and its use in major depressive and bipolar disorders, has been suggested. However, the molecular mechanisms underlying this possible effect are still unknown. The present review firstly summarizes the structure-activity relationship studies and the mechanism of action of modafinil and its related compounds. Then, it focuses on data demonstrating that modafinil interacts with serotonin neuronal activity in rat frontal cortex and dorsal raphe nucleus, two brain areas linked together and involved in depression. Preclinical and clinical evidence of a positive interaction between modafinil and classical antidepressant drugs, is also summarized.
Keywords: Structure-activity relationship, animal and human studies, frontal cortex, dorsal raphe nucleus and hippocampus, major depression and bipolar disorder, microdialysis, adrafinil, antidepressant, modafinilic acid
Mini-Reviews in Medicinal Chemistry
Title:The Vigilance Promoting Drug Modafinil Modulates Serotonin Transmission in the Rat Prefrontal Cortex and Dorsal Raphe Nucleus. Possible Relevance for Its Postulated Antidepressant Activity
Volume: 13 Issue: 4
Author(s): Luca Ferraro, Tiziana Antonelli, Sarah Beggiato, Maria Cristina Tomasini, Kjell Fuxe and Sergio Tanganelli
Affiliation:
Keywords: Structure-activity relationship, animal and human studies, frontal cortex, dorsal raphe nucleus and hippocampus, major depression and bipolar disorder, microdialysis, adrafinil, antidepressant, modafinilic acid
Abstract: Modafinil, (RS)-2-(diphenylmethylsulfinyl)acetamide derivative (Modiodal, Provigil), is a vigilance-promoting agent which reduces sleep episodes by improving wakefulness. It is approved by the USA FDA for narcolepsy, shiftwork sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure. Unlike classical psychostimulants such as amphetamine and amphetamine-like compounds, the awaking effect of modafinil is not associated with a disturbance of nighttime sleep, tolerance, and sensitization. Its precise mechanism of action is still unclear. In animal studies, modafinil and its analogues have been shown to modify dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic pathways. Besides the approved use in sleep disorders, modafinil has been investigated for the treatment of fatigue, impaired cognition and some symptoms in a number of other disorders. In particular, clinical studies seem to indicate that the drug could be particularly successful in the treatment of depression and its use in major depressive and bipolar disorders, has been suggested. However, the molecular mechanisms underlying this possible effect are still unknown. The present review firstly summarizes the structure-activity relationship studies and the mechanism of action of modafinil and its related compounds. Then, it focuses on data demonstrating that modafinil interacts with serotonin neuronal activity in rat frontal cortex and dorsal raphe nucleus, two brain areas linked together and involved in depression. Preclinical and clinical evidence of a positive interaction between modafinil and classical antidepressant drugs, is also summarized.
Export Options
About this article
Cite this article as:
Ferraro Luca, Antonelli Tiziana, Beggiato Sarah, Cristina Tomasini Maria, Fuxe Kjell and Tanganelli Sergio, The Vigilance Promoting Drug Modafinil Modulates Serotonin Transmission in the Rat Prefrontal Cortex and Dorsal Raphe Nucleus. Possible Relevance for Its Postulated Antidepressant Activity, Mini-Reviews in Medicinal Chemistry 2013; 13 (4) . https://dx.doi.org/10.2174/1389557511313040002
DOI https://dx.doi.org/10.2174/1389557511313040002 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
Related Articles
-
Latest Advances in Hydrogel-Based Drug Delivery Systems for Optimization of Metabolic Syndrome Treatment
Current Medicinal Chemistry subject Index To Volume 3
Current Protein & Peptide Science Corticotropin-Releasing Factor Receptor Antagonists in Affective Disorders and Drug Dependence - An Update
CNS & Neurological Disorders - Drug Targets Extracts and Flavonoids of <i>Passiflora</i> Species as Promising Anti-inflammatory and Antioxidant Substances
Current Pharmaceutical Design Microsomal Prostaglandin E Synthase: A Key Enzyme in PGE2 Biosynthesis and Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Glucocorticoid Receptor Interacting Co-regulators: Putative Candidates for Future Drug Targeting Therapy
Mini-Reviews in Medicinal Chemistry An Indirect Screen for Brain Uptake of 1,2-Diarylethane Melanocortin 4 Receptor Antagonists in Rats
Drug Metabolism Letters Integrative Physiology of Orexins and Orexin Receptors
CNS & Neurological Disorders - Drug Targets Keeping Obesity and Metabolic Syndrome at Bay with Central Leptin and Cytokine Gene Therapy
Current Medicinal Chemistry - Central Nervous System Agents Nutritional Support in Cancer
Current Nutrition & Food Science Metabolic Features Across the Female Life Span in Women with PCOS
Current Pharmaceutical Design Glucose Control and Use of Continuous Glucose Monitoring in the Intensive Care Unit: A Critical Review
Current Diabetes Reviews Ex Vivo Proton NMR Analysis and Characterization of Thymus Lipid Metabolites and their Variation with Age in C57BL/6 Mice
Current Aging Science Effects of Mindfulness on Diabetes Mellitus: Rationale and Overview
Current Diabetes Reviews Manganese Enhanced Magnetic Resonance Imaging
Current Pharmaceutical Biotechnology Glutamate: The New Frontier in Pharmacotherapy for Cocaine Addiction
CNS & Neurological Disorders - Drug Targets Pharmacotherapy for Obesity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Interactions Between Growth Hormone and the Thyroid Gland - with Special Reference to Biochemical Diagnosis
Current Medicinal Chemistry Viruses in Semen and Male Genital Tissues - Consequences for the Reproductive System and Therapeutic Perspectives
Current Pharmaceutical Design Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment
Current Pharmaceutical Design