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Lili Zong, Chao Wang, Adhitya Mangala Putra Moeljadi, Xinyi Ye, Rakesh Ganguly, Yongxin Li, Hajime Hirao, Choon-Hong Tan
Catalytic use of peroxomolybdate for asymmetric transformations has attracted increasing attention due to its catalytic properties and application in catalysis. Herein, we report chiral bisguanidinium dinuclear oxodiperoxomolybdosulfate [BG](2+)[(μ-SO4)Mo2O2(μ-O2)2(O2)2](2-) ion pair, as a catalyst for enantioselective sulfoxidation using aqueous H2O2 as the terminal oxidant. The ion pair catalyst is isolatable, stable and useful for the oxidation of a range of dialkyl sulfides. The practical utility was illustrated using a gram-scale synthesis of armodafinil, a commercial drug, with the catalyst generated in situ from 0...
November 21, 2016: Nature Communications
Andrew D Krystal, Xavier A Preud'homme
STUDY OBJECTIVES: Nocturia, voids which disturb sleep, is the most common cause of awakenings and is associated with daytime sleepiness. Because the standard treatments for the most common causes of nocturia are relatively ineffective, many treated patients with nocturia are left with residual sleepiness. We carried out this pilot study to evaluate the potential of Armodafinil to be an effective means of addressing the sleepiness that persists in many nocturia patients despite their receiving standard therapy...
September 9, 2016: Sleep
Lucie Barateau, Régis Lopez, Yves Dauvilliers
Narcolepsy type 1 (NT1) and type 2 (NT2) are two rare neurological diseases, classified as central disorders of hypersomnolence. The pathophysiology of NT1 is well known; it is caused by the selective destruction of hypocretin (Hcrt) neurons, by a highly suspected autoimmune process. On the contrary, little is known about NT2 etiology, sharing with NT1 somnolence and signs of dysregulation of rapid eye movement (REM) sleep, but not cataplexy. Management strategies are rather codified, at least in adults, with a lifelong treatment required in NT1, whereas no pharmacological study focused only on NT2 patients, with sometimes spontaneous improvement or disappearance of their symptoms...
October 2016: Current Treatment Options in Neurology
Maddalena Mereu, Lauren E Chun, Thomas E Prisinzano, Amy H Newman, Jonathan L Katz, Gianluigi Tanda
Blockade of dopamine (DA) reuptake via the dopamine transporter (DAT) is a primary mechanism identified as underlying the therapeutic actions of (±)-modafinil (modafinil) and its R-enantiomer, armodafinil. Herein, we explored the neurochemical and behavioral actions of modafinil to better characterize its psychostimulant profile. Swiss-Webster mice were implanted with microdialysis probes in the nucleus accumbens shell (NAS) or core (NAC) to evaluate changes in DA levels related to acute reinforcing actions of drugs of abuse...
January 2017: European Journal of Neuroscience
Julia L Chapman, Yasmina Serinel, Nathaniel S Marshall, Ronald R Grunstein
Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA), but it is also common in the general population. When sleepiness remains after continuous positive airway pressure (CPAP) treatment of OSA, comorbid conditions or permanent brain injury before CPAP therapy may be the cause of the residual sleepiness. There is currently no broad approach to treating residual EDS in patients with OSA. Individual assessment must be made of comorbid conditions and medications, and of lifestyle factors that may be contributing to the sleepiness...
September 2016: Sleep Medicine Clinics
Chris Atkins, Andrew M Wilson
Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients...
August 9, 2016: Chronic Respiratory Disease
Susan Willavize, Jill Fiedler-Kelly, Elizabeth Ludwig, Lingling Guan
Population pharmacokinetic models for armodafinil and its major metabolites, R-modafinil acid and modafinil sulfone, were developed, and selected covariates were investigated. Data from 583 healthy subjects and patients with bipolar I disorder in 11 phase 1-3 studies (8027 concentrations) of armodafinil, given as single or multiple once-daily doses (50- to 400-mg tablet or capsule), were pooled. A previously developed 1-compartment model with first-order absorption without covariate effects was initially applied to pooled phase 1 and 2 data...
February 2017: Journal of Clinical Pharmacology
Sheila N Garland, Joseph A Roscoe, Charles E Heckler, Holly Barilla, Philip Gehrman, James C Findley, Anita R Peoples, Gary R Morrow, Charles Kamen, Michael L Perlis
STUDY OBJECTIVES: This study involves the analysis of a secondary outcome of a trial examining whether cognitive behavior therapy for insomnia (CBT-I), a wake-promoting medication (armodafinil), or both results in greater improvement in prospectively assessed sleep continuity and daytime sleepiness than a placebo-alone group among a heterogeneous group of cancer survivors. Whether or not armodafinil alone, and/or when combined with CBT-I, affected adherence with CBT-I was evaluated. DESIGN: This study is a randomized, placebo-controlled, clinical trial...
April 2016: Sleep Medicine
Lucie Barateau, Régis Lopez, Yves Dauvilliers
Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom...
May 2016: CNS Drugs
Terence A Ketter, Jess Amchin, Mark A Frye, Nicholas Gross
BACKGROUND: Safe/well-tolerated treatments for bipolar I depression remain limited. We assessed safety/tolerability of adjunctive open-label armodafinil, a wakefulness-promoting agent evaluated in 3 acute, controlled efficacy studies with variable efficacy results. METHODS: Completers of three 8-week, double-blind, placebo-controlled adjunctive armodafinil studies (150-200 mg/day added to ongoing stable maintenance doses of 1 or 2 protocol-defined mood stabilizers) in bipolar I depression could enter this 6-month, open-label extension study...
June 2016: Journal of Affective Disorders
Yi-Chun Kuan, Dean Wu, Kuang-Wei Huang, Nai-Fang Chi, Chaur-Jong Hu, Chen-Chih Chung, Ka-Wai Tam, Yao-Hsien Huang
PURPOSE: Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents known to be effective in alleviating sleepiness. METHODS: We performed a systematic review and meta-analysis of data from published randomized controlled trials (RCTs) that evaluated the efficacy of modafinil and armodafinil in treating EDS in patients with OSA...
April 2016: Clinical Therapeutics
B Ramachandra
Modafinil is a synthetic molecule used for the treatment of narcolepsy. Narcolepsy is a neurological disorder, due to which people experience frequent excessive daytime sleepiness (EDS). Nevertheless, there are some concerns about modafnil quality control. The modafinil enantiomers are both biologically active. However, it has been reported that the pharmacological properties of the both enantiomers are different and that the S-enantiomer is eliminated three times faster than the R-enantiomer. Therefore, most of the pharmaceutical companies have shifted to produce armodafinil (R-enantiomer) instead of the racemate...
November 2016: Critical Reviews in Analytical Chemistry
Gin S Malhi, Yulisha Byrow, Darryl Bassett, Philip Boyce, Malcolm Hopwood, William Lyndon, Roger Mulder, Richard Porter, Ajeet Singh, Greg Murray
The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression--specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants...
March 2016: Australian and New Zealand Journal of Psychiatry
Eudocia Q Lee, Alona Muzikansky, Jan Drappatz, Santosh Kesari, Eric T Wong, Camilo E Fadul, David A Reardon, Andrew D Norden, Lakshmi Nayak, Mikael L Rinne, Brian M Alexander, Nils D Arvold, Lisa Doherty, Jennifer Stefanik, Debra LaFrankie, Sandra F Ruland, Julee Pulverenti, Katrina H Smith, Sarah C Gaffey, Samantha Hammond, Patrick Y Wen
BACKGROUND: Fatigue is common among glioma patients undergoing radiotherapy (RT) and impacts quality of life (QOL). We evaluated whether armodafinil, a wakefulness-promoting medication, improves fatigue in glioma patients undergoing RT. METHODS: Eligibility criteria included age ≥18 years, Karnofsky performance status ≥60, and grade 2-4 glioma undergoing RT to a total dose of 50-60 Gy. Patients were randomized 1:1 to armodafinil or placebo for 8 weeks beginning within 10 days of starting RT...
June 2016: Neuro-oncology
Julia L Chapman, Andrew Vakulin, Jan Hedner, Brendon J Yee, Nathaniel S Marshall
Modafinil is used internationally to treat residual sleepiness despite continuous positive airway pressure in obstructive sleep apnoea (res-OSA). In 2011, the European Medicines Agency removed the indication based on an unfavourable risk-benefit profile in two trials for efficacy and all accumulated safety data. We performed a meta-analysis of all randomised controlled trials of modafinil (or armodafinil) in res-OSA to quantify efficacy and safety.We systematically searched and assessed studies from major databases, conferences and trials registries to find randomised, placebo-controlled trials of modafinil/armodafinil for ≥2 weeks in adult res-OSA treating sleepiness...
May 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Chittaranjan Andrade
Modafinil or armodafinil (ar/mod) may be considered for patients with approved or unapproved indications, including excessive daytime drowsiness, fatigue, attention-deficit/hyperactivity disorder (ADHD), or addictions. Ar/mod is classified as a psychostimulant, and psychostimulants have been associated with a small risk of seizures. There is no guidance about the use of ar/mod in patients who are at risk of seizures. This article suggests how a physician may explore the safety of ar/mod if indicated in a patient at such risk...
January 2016: Journal of Clinical Psychiatry
Chittaranjan Andrade
Modafinil or armodafinil (ar/mod) augmentation of antipsychotic medication in schizophrenia patients may be considered with a view to reduce negative symptoms associated with the illness or excessive daytime drowsiness due to any cause. The available data suggest that there is no role for ar/mod in reducing negative symptom burden. A recent pharmacokinetic (PK) study suggested that armodafinil (250 mg/d) reduces key PK parameters of risperidone by about 50%, and key PK parameters of 9-hydroxyrisperidone (paliperidone) by about 20%-30%, probably through induction of CYP3A4...
December 2015: Journal of Clinical Psychiatry
Jason M Jerry, Nicole Shirvani, Roman Dale
No abstract text is available yet for this article.
February 2016: Journal of Clinical Psychopharmacology
Charles E Heckler, Sheila N Garland, Anita R Peoples, Michael L Perlis, Michelle Shayne, Gary R Morrow, Charles Kamen, Jenine Hoefler, Joseph A Roscoe
PURPOSE: Fatigue is a prevalent, distressing side effect of cancer and cancer treatment which commonly coexists with insomnia. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia in cancer patients, but less is known about its ability to impact fatigue. This work is the analysis for a secondary aim of a four-arm randomized controlled trial (RCT) study assessing the combined and comparative effect of CBT-I and a wakefulness-promoting agent, armodafinil (A), to improve sleep and daytime functioning in cancer survivors...
May 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Mona Darwish, Mary Bond, Ronghua Yang, Edward T Hellriegel, Philmore Robertson
BACKGROUND AND OBJECTIVE: Patients with bipolar I disorder and schizophrenia have an increased risk of obstructive sleep apnea. The effects of armodafinil, a weak cytochrome P450 (CYP) 3A4 inducer, on pharmacokinetics and safety of risperidone, an atypical antipsychotic used to treat major psychiatric illness, were investigated. METHODS: Healthy subjects received 2 mg risperidone alone and after armodafinil pretreatment (titrated to 250 mg/day). Pharmacokinetic parameters were derived from plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone (formed via CYP2D6 and CYP3A4), collected before and over 4 days after risperidone administration, and from steady-state plasma concentrations of armodafinil and its circulating metabolites, R-modafinil acid and modafinil sulfone...
November 2015: Clinical Drug Investigation
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