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Clinical Pharmacology and Therapeutics Feb 2024
PubMed: 38108195
DOI: 10.1002/cpt.3142 -
Pediatric Research Apr 2024The aim of this scoping review is to examine the extent and depth of the literature on effects of central nervous system (CNS) stimulant medications on physical function... (Review)
Review
The aim of this scoping review is to examine the extent and depth of the literature on effects of central nervous system (CNS) stimulant medications on physical function in children with cerebral palsy (CP). A systematic search for relevant peer-reviewed studies was conducted of PubMed, CINAHL, Cochrane, SPORTDiscus, Embase, & Scopus (January 2002 & August 2022). We included studies that examined the effects of CNS stimulants on physical function in children with CP. Four studies met our selection criteria. All studies explored the effect of Modafinil on physical function outcomes. Three studies of the four included studies reported positive effects of Modafinil on spasticity, motor performance, and gait, whereas one study reported no significant effects of Modafinil. Our findings suggest that there is very low-quality evidence that suggests that Modafinil may enhance physical improvements in body structure and function, including reduction in spasticity and improvements in gait parameters. IMPACT: Central nervous system stimulants were examined for efficacy on physical function and spasticity in children with cerebral palsy. The evidence on the effects of central nervous system stimulants on physical function in children with CP is limited and inconsistent.
Topics: Child; Humans; Central Nervous System Stimulants; Cerebral Palsy; Gait; Modafinil; Muscle Spasticity; Treatment Outcome
PubMed: 38071277
DOI: 10.1038/s41390-023-02933-3 -
International Journal of Molecular... Nov 2023-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue...
-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue distribution profiles, with a specific focus on central nervous system distribution and metabolism, of -CE-123 and -modafinil. To address this objective, a precise liquid chromatography-high resolution mass spectrometry method was developed and partially validated. Neuropharmacokinetic parameters were assessed using the Combinatory Mapping Approach. Our findings reveal distinct differences between the two compounds. Notably, -CE-123 demonstrates a significantly superior extent of transport across the blood-brain barrier (BBB), with an unbound brain-to-plasma concentration ratio (K) of 0.5, compared to -modafinil's K of 0.1. A similar pattern was observed for the transport across the blood-spinal cord barrier. Concerning the drug transport across cellular membranes, we observed that -CE-123 primarily localizes in the brain interstitial space, whereas -modafinil distributes more evenly across both sides of the plasma membrane of the brain's parenchymal cells (K). Furthermore, our study highlights the substantial differences in hepatic metabolic stability, with -CE-123 having a 9.3-fold faster metabolism compared to -modafinil. In summary, the combination of improved BBB transport and higher affinity of -CE-123 to dopamine transporters in comparison to -modafinil makes -CE-123 a promising candidate for further testing for the treatment of cognitive decline.
Topics: Benzhydryl Compounds; Brain; Central Nervous System; Dopamine Plasma Membrane Transport Proteins; Modafinil
PubMed: 38069277
DOI: 10.3390/ijms242316956 -
Environmental Science and Pollution... Jan 2024Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study...
Selenium alleviates modafinil-induced neurobehavioral toxicity in rat via PI3K/Akt/mTOR/GSK3B signaling pathway and suppression of oxidative stress and apoptosis: in vivo and in silico study.
Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study aims to determine the probable MOD brain toxicity and elucidate the possible role of selenium (Se) in ameliorating the neurotoxicity in rat models. Fifty-four male Albino rats were randomly assigned into nine groups. The groups were G1 (control negative), G2 (Se0.1), G3 (Se0.2), G4 (MOD300), G5 (MOD600), G6 (Se0.1 + MOD300), G7 (Se0.2 + MOD300), G8 (Se0.1 + MOD600), and G9 (Se0.2 + MOD600). After finishing the experiment, blood and brain tissue were harvested for biochemical and histological investigation. Neurobehavior parameters were assessed. Tissue neurotransmitter levels and oxidative stress markers were assessed. Gene expression of PI3K/Akt/mTOR-GSK3B, orexin, and orexin receptor2 was measured by qRT-PCR. Histological and immunohistochemistry assessments, as well as molecular docking, were carried out. MOD-induced neurobehavioral toxicity exhibited by behavioral and cognitive function impairments, which are associated with decreased antioxidant activities, increased MDA levels, and decreases in neurotransmitter levels. Brain levels of mRNA expression of PI3K, Akt, and mTOR were decreased, while GS3K, orexin, and orexin receptors were significantly elevated. These disturbances were confirmed by histopathological brain changes with increased silver and Bax immunostaining and decreased crystal violet levels. MOD induced neurotoxic effects in a dose-dependent manner. Compared with the MOD groups, SE coadministration significantly attenuates MOD-induced toxic changes. Docking study shows the protective role of Se as an apoptosis inhibitor and inflammation inhibitor. In conclusion, Se could be used as a biologically effective antioxidant compound to protect from MOD neurobehavioral toxicity in Wistar rats by reversing behavioral alterations, inflammation, apoptosis, and oxidative injury.
Topics: Humans; Rats; Male; Animals; Selenium; Proto-Oncogene Proteins c-akt; Antioxidants; Phosphatidylinositol 3-Kinases; Modafinil; Orexins; Molecular Docking Simulation; Rats, Wistar; Signal Transduction; TOR Serine-Threonine Kinases; Oxidative Stress; Inflammation; Apoptosis; Neurotransmitter Agents; Glycogen Synthase Kinase 3 beta
PubMed: 38015391
DOI: 10.1007/s11356-023-31093-4 -
Physical Medicine and Rehabilitation... Feb 2024Pharmacologic treatment of disorders of consciousness remains a critical but challenging task for clinicians. Amantadine has been shown to promote the rate of neurologic... (Review)
Review
Pharmacologic treatment of disorders of consciousness remains a critical but challenging task for clinicians. Amantadine has been shown to promote the rate of neurologic recovery for patients with traumatic disorders of consciousness when administered between 4 and 16 weeks, as demonstrated by a well-designed randomized control trial. While there are no large, randomized controlled trials to support the use of other dopaminergic medicines (bromocriptine, levodopa, apomorphine), there is a large body of literature implicating their role in improving alertness and responsiveness in disorders of consciousness. Zolpidem can increase the level of consciousness in a small subset of patients. Zolpidem and intrathecal baclofen likely increase the level of consciousness via the mesocircuit pathway. Psychostimulant medications can be initiated in patients, even without strong evidence to support their use, as long as basic principles of brain injury medicine are followed, and there are systems in place to evaluate therapeutic response.
Topics: Humans; Consciousness; Zolpidem; Consciousness Disorders; Brain Injuries; Amantadine; Randomized Controlled Trials as Topic
PubMed: 37993186
DOI: 10.1016/j.pmr.2023.06.023 -
Clinical NeuropharmacologyAcute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can...
OBJECTIVES
Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs.
METHODS
This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects.
CONCLUSIONS
The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.
Topics: Humans; Modafinil; Consciousness; Brain Injuries, Traumatic; Amantadine; Brain Injuries; Randomized Controlled Trials as Topic
PubMed: 37962310
DOI: 10.1097/WNF.0000000000000577 -
Scientific Reports Nov 2023The use of so-called 'smart drugs' such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have... (Randomized Controlled Trial)
Randomized Controlled Trial
The use of so-called 'smart drugs' such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have limited user enthusiasm. Open-label placebo (OLP) treatment, i.e., inert treatments that are openly disclosed to individuals as having no active pharmacological ingredient, has been shown to improve various medical symptoms and conditions, including those related to cognitive performance. OLP treatment could therefore be an exciting alternative to pharmacological cognitive enhancers. Here, we used a randomized-controlled design to investigate the effect of a 21-day OLP treatment on several sub-domains of cognitive performance in N = 78 healthy volunteers. Subjective and objective measures of cognitive performance as well as different measures of well-being were obtained before and after the treatment period. Using a combination of classic Frequentist and Bayesian analysis approaches showed no additional benefit from OLP treatment in any of the subjective or objective measures of cognitive performance. Our study thus highlights possible limitations of OLP treatment in boosting cognitive performance in healthy volunteers. These findings are discussed in the light of expectancy-value considerations that may determine OLP efficacy.
Topics: Humans; Attention; Bayes Theorem; Cognition; Healthy Volunteers; Modafinil; Placebo Effect
PubMed: 37945662
DOI: 10.1038/s41598-023-45979-3 -
Purinergic Signalling Nov 2023Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression...
Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression contributes to the development of fibrotic diseases and whether AAR and AAR upregulation inhibits fibrotic responses. Primary human lung fibroblasts (HLFs) from normal (NHLFs) or patients with idiopathic pulmonary fibrosis (DHLF) were used for in vitro testing. Murine models of fibrotic liver or pulmonary disease were developed by injecting thioacetamide intraperitoneally, by feeding a high-fat diet, or by intratracheal instillation of bleomycin. Modafinil, which activates cAMP signaling via AAR and AAR, was administered orally. The protein amounts of AAR, AAR, and exchange protein directly activated by cAMP (Epac) were reduced, while collagen and α-smooth muscle actin (α-SMA) were elevated in DHLFs compared to NHLFs. In liver or lung tissue from murine models of fibrotic diseases, AAR and AAR were downregulated, but AAR and AAR were not. Epac amounts decreased, and amounts of collagen, α-SMA, K2.3, and K3.1 increased compared to the control. Modafinil restored the amounts of AAR, AAR, and Epac, and reduced collagen, α-SMA, K2.3, and K3.1 in murine models of fibrotic diseases. Transforming growth factor-β reduced the amounts of AAR, AAR, and Epac, and elevated collagen, α-SMA, K2.3, and K3.1 in NHLFs; however, these alterations were inhibited by modafinil. Our investigation revealed that AAR and AAR downregulation induced liver and lung fibrotic diseases while upregulation attenuated fibrotic responses, suggesting that AAR and AAR-upregulating agents, such as modafinil, may serve as novel therapies for fibrotic diseases.
PubMed: 37938538
DOI: 10.1007/s11302-023-09973-8 -
Journal of Clinical Sleep Medicine :... Mar 2024This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical...
UNLABELLED
This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical significance of this report lies in the fact that armodafinil is known to cause headaches, at least initially. But perhaps through a reduced need for caffeine and/or a regulation of sleep/wake, armodafinil may reduce headache frequency and severity.
CITATION
Barone DA. Headache improves with armodafinil. 2024;20(3):469-470.
Topics: Humans; Modafinil; Narcolepsy; Caffeine; Cataplexy; Headache
PubMed: 37921201
DOI: 10.5664/jcsm.10906