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.
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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 |
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