Chronic methylphenidate induces increased quinone production and subsequent depletion of the antioxidant glutathione in the striatum

Oakes, Hannah; Ketchem, Shannon; Hall, Alexis; Ensley, Tucker; Archibald, Kristen M.; Pond, Brooks B.

doi:10.1016/j.pharep.2019.08.003

Cited by 6 publications

(2 citation statements)

References 19 publications

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“…The first reason we propose is related to possible changes in DA receptors that modulate the response to MPH: in murine models, D1 and D2 receptors were suggested to play a synergistic role in the sensitization to the therapeutic effects exerted by MPH [ 74 ]; thereby, a significant increase in S100B values in the first months after therapy could be linked to MPH-induced overactivation of D2 receptors, given the capacity of S100B to bind this receptor and potentiate its activity [ 75 , 76 ]. A second explanation could be associated with the excess of DA possibly generated by MPH, which has been reported to lead to reactive oxygen species (ROS) production and depletion of the antioxidant glutathione in preclinical studies [ 77 , 78 , 79 ]. According to this, MPH administration might have originated an initial inflammatory response involving S100B [ 24 , 25 , 26 , 27 ] in our patients as a consequence of the increase in DA levels.…”

Section: Discussionmentioning

confidence: 99%

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs

et al. 2023

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Background: Increasing evidence supports a neuroinflammatory basis in ADHD damaging glial function and thereby altering dopaminergic (DA) neurotransmission. Previous studies focusing on the S100B protein as a marker of glial function have shown contradictory results. We conducted a clinical trial to investigate differences in S100B levels between ADHD patients and controls, as well as observe gradual changes in S100B concentrations after a triple therapy (TT) containing methylphenidate (MPH), melatonin (aMT) and omega-3 fatty acids (ω-3 PUFAs). Methods: 62 medication-naïve children with ADHD (ADHD-G) and 65 healthy controls (C-G) were recruited. Serum S100B was measured at baseline (T0) in ADHD-G/C-G, and three (T3) and six months (T6) after starting TT in the ADHD-G, together with attention scores. Results: A significant increase in S100B was observed in the ADHD-G vs. C-G. In the ADHD-G, significantly higher S100B values were observed for comparisons between T0–T3 and between T0–T6, accompanied by a significant improvement in attention scores for the same timepoint comparisons. No significant differences were found for S100B between T3–T6. Conclusion: Our results agree with the hypothesis of glial damage in ADHD. Further studies on the link between DA and S100B are required to explain the transient increase in S100B following TT.

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Section: Discussionmentioning

confidence: 99%

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs

et al. 2023

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“…107 Oakes and colleagues at East Tennessee State University recently described a dose-dependent elevation in striatal dopaminergic neuronal DA-quinone production with chronic MPH exposure in a murine model. 108 As the neuroimmune cascade is activated by oxidative stress, glutathione conjugates with the DA-quinone and sequesters it. Unfortunately, as glutathione reserves are depleted by chronic use, greater oxidative stress occurs.…”

Section: Molecular-mphmentioning

confidence: 99%

Prescription Stimulant-Induced Neurotoxicity: Mechanisms, outcomes, and relevance to ADHD

Tucker

2021

Michigan Journal of Medicine

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Attention-deficit/hyperactivity disorder (ADHD) is a relatively prevalent neuropsychiatric and neurodevelopmental condition characterized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ) as difficulty sustaining attention and maintaining tasks at hand, heightened distractibility, and other deficits in executive functioning. Prescription stimulants—amphetamine (AMP) and methylphenidate (MPH)—are the first-line treatment(s) for ADHD in both pediatric and adult populations and exist in many formulations. Troublingly, the non-medical use (NMU) of amphetamine and methylphenidate is more prevalent in the American population, especially on college and university campuses, than the condition of interest. The neurotoxicological profile and NMU epidemiology of prescription stimulants is of direct relevance to primary care physicians and psychiatrists as they are the providers most frequently tasked with the treatment of ADHD and the surveillance of substance misuse behaviors in the young adult population. As comprehensive literature reviews of the mechanisms and potential adverse sequelae of prescription stimulant-induced neurotoxicity intended for medical clinicians have been quite sparse in the last decade—especially given the gravity of the issue—this article includes a brief primer on ADHD etiology and pathophysiology; considers the current state of NMU epidemiology; reviews the mechanisms of action of AMP and MPH; and, finally, summarizes known molecular and clinical manifestations of AMP and MPH neurotoxicity.

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Methylphenidate and Rosmarinus officinalis improves cognition and regulates inflammation and synaptic gene expression in AlCl3-induced neurotoxicity mouse model

et al. 2020

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Chronic methylphenidate induces increased quinone production and subsequent depletion of the antioxidant glutathione in the striatum

Cited by 6 publications

References 19 publications

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs

Prescription Stimulant-Induced Neurotoxicity: Mechanisms, outcomes, and relevance to ADHD

Methylphenidate and Rosmarinus officinalis improves cognition and regulates inflammation and synaptic gene expression in AlCl3-induced neurotoxicity mouse model

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