Simple Synthesis of Modafinil Derivatives and Their Anti-inflammatory Activity

Jung, Jaehan; Lee, Yeon-Ju; Son, Jee Young; Lim, Eunyoung; Jung, Mankil; Oh, Seikwan

doi:10.3390/molecules170910446

Cited by 34 publications

(22 citation statements)

References 22 publications

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“…However, several other drugs with anti-inflammatory properties may additional yield antidepressant treatment effects. Statins [ 52 ], poly-unsatturated fatty acids [ 53 ], pioglitazone [ 54 ], corticosteroids, minocycline [ 55 ], and modafinil [ 56 ] have anti-inflammatory properties and studies have associated these drugs with potential antidepressant treatment effects.…”

Section: Review Of Anti-inflammatory Agents and Potential Antidepressmentioning

confidence: 99%

“…Finally, another emerging drug is the anti-epileptic drug modafinil, which has been associated with anti-inflammatory properties [ 56 ] and furthermore shown effective antidepressant effects in augmentation strategies for acute depressive episodes, including symptoms of fatigue, in both unipolar and bipolar disorders [ 67 , 68 ]. However, due to several side effects, cautious use of modafinil is recommended [ 69 ].…”

Section: Review Of Anti-inflammatory Agents and Potential Antidepressmentioning

confidence: 99%

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Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

Köhler

Krogh²,

Mors³

et al. 2016

439

280

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Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity of the inflammatory cascade, limited clinical evidence, and the risk for side effects stress cautiousness before clinical application. Thus, despite proof-of-concept studies of anti-inflammatory treatment effects in depression, important challenges remain to be investigated. Within this paper, we review the association between inflammation and depression together with the current evidence on use of anti-inflammatory treatment in depression. Based on this, we address the questions and challenges that seem most important and relevant to future studies, such as timing, most effective treatment lengths and identification of subgroups of patients potentially responding better to different anti-inflammatory treatment regimens.

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Section: Review Of Anti-inflammatory Agents and Potential Antidepressmentioning

confidence: 99%

Section: Review Of Anti-inflammatory Agents and Potential Antidepressmentioning

confidence: 99%

Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

Köhler

Krogh²,

Mors³

et al. 2016

439

280

View full text Add to dashboard Cite

show abstract

“…Modafinil is a novel anti-epileptic and wakefulness-promoting drug, which has also been associated with anti-inflammatory properties [ 210 ]. There are several studies that demonstrated the beneficial effects of modafinil on depression-like behavior in both animal models and clinical trials (Table 2 ).…”

Section: Effects Of Anti-inflammatory Drugs On Depressive Symptomsmentioning

confidence: 99%

Therapeutic Strategies for Treatment of Inflammation-related Depression

et al. 2018

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Background:Mounting evidence demonstrates enhanced systemic levels of inflammatory mediators in depression, indicating that inflammation may play a role in the etiology and course of mood disorders. Indeed, proinflammatory cytokines induce a behavioral state of conservation-withdrawal resembling human depression, characterized by negative mood, fatigue, anhedonia, psychomotor retardation, loss of appetite, and cognitive deficits. Neuroinflammation also contributes to non-responsiveness to current antidepressant (AD) therapies. Namely, response to conventional AD medications is associated with a decrease in inflammatory biomarkers, whereas resistance to treatment is accompanied by increased inflammation.Methods:In this review, we will discuss the utility and shortcomings of pharmacologic AD treatment strategies focused on inflammatory pathways, applied alone or as an adjuvant component to current AD therapies.Results:Mechanisms of cytokine actions on behavior involve activation of inflammatory pathways in the brain, resulting in changes of neurotransmitter metabolism, neuroendocrine function, and neuronal plasticity. Selective serotonin reuptake inhibitors exhibit the most beneficial effects in restraining the inflammation markers in depression. Different anti-inflammatory agents exhibit AD effects via modulating neurotransmitter systems, neuroplasticity markers and glucocorticoid receptor signaling. Anti-inflammatory add-on therapy in depression highlights such treatment as a candidate for enhancement strategy in patients with moderate-to-severe depression.Conclusion:The interactions between the immune system and CNS are not only involved in shaping behavior, but also in responding to therapeutics. Even though, substantial evidence from animal and human research support a beneficial effect of anti-inflammatory add-on therapy in depression, further research with special attention on safety, particularly during prolonged periods of anti-inflammatory co-treatments, is required.

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“…Besides, modafinil derivatives exert anti-inflammatory effects much better than aspirin via decreasing iNOS and COX-2 in LPS-treated BV2 microglia cells. Modafinil can also inhibit the apoptosis and autophagy in rapamycin-induced hippocampal neuronal cells (Jung et al 2012). Furthermore, the systematic review indicates the procognitive effects of modafinil on major depressive disorder (Cao et al 2019).…”

Section: Introductionmentioning

confidence: 98%

Modafinil ameliorated pancreatic injury and inflammation through upregulating SNIP1

Qin

et al. 2020

gpb

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Acute pancreatitis (AP) is the inflammatory response of the exocrine pancreas to various causes. Modafinil has significant anti-inflammation and anti-oxidation effects. No experiment has assessed the effects of modafinil on AP. Thus, the study aims to study the effects of modafinil on AP and its potential mechanism in vivo and vitro. 5% sodium taurocholate was retrograde injected into pancreatic duct to establish AP rat model. The severity of AP was detected by H&E staining, serum amylase and lipase levels. The inflammation, oxidative stress and apoptosis were detected separately by ELISA, MDA and SOD kits, tunnel staining and Western blotting in rats. Besides, SNIP1 expression was analyzed by qPCR and Western blotting. In vivo, AR42J cells were stimulated by cerulein and lipopolysaccharide to establish AP cell model. Flow cytometry examined cell apoptosis. After the plasmids silencing SNIP1 were transfected into AP cells, the inhibitory effects of modafinil on inflammation, oxidative stress and apoptosis were significantly reversed. The results indicated that modafinil showed significant curative and therapeutic effects by regulating SNIP1 levels.

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Simple Synthesis of Modafinil Derivatives and Their Anti-inflammatory Activity

Cited by 34 publications

References 22 publications

Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

Therapeutic Strategies for Treatment of Inflammation-related Depression

Modafinil ameliorated pancreatic injury and inflammation through upregulating SNIP1

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