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Geraldine Dowling, Pierce V Kavanagh, Brian Talbot, John O'Brien, Gary Hessman, Gavin McLaughlin, Brendan Twamley, Simon D Brandt
2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy. Increasing popularity and off-label use as a cognitive enhancer has resulted in a reputation as an intelligence boosting 'wonder drug'. Common alternatives available from online shops and other retail outlets include 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide (adrafinil), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}acetamide (CRL-40,940), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide (CRL-40,941), and N-methyl-4,4-difluoro-modafinil (modafiendz), respectively...
March 2017: Drug Testing and Analysis
Mehmet Gokhan Caglayan, Sara Sheykhi, Lorenzo Mosca, Pavel Anzenbacher
Recognition of electroneutral Lewis bases and anions in aqueous media is extremely difficult. We show that fluorescent coordinatively unsaturated metal complexes can recognize various Lewis bases while providing an easy-to-detect fluorescence response. This approach is applied to the detection of adrafinil, a banned performance-enhancing drug.
July 7, 2016: Chemical Communications: Chem Comm
Lyndsey M Killian, James R Docherty
Stimulants are banned in competition by the World Anti-Doping Agency, except for a small number of therapeutic agents subject to monitoring, including bupropion. We have examined the potency of bupropion in comparison with two agents banned in competition, adrafinil and modafinil, and with cocaine and desipramine as blockers of the noradrenaline re-uptake transporter in peripheral tissues of the rat. For studies in vivo, the pressor response to noradrenaline in the anaesthetized rat was studied. Cocaine, desipramine and bupropion at doses of 0...
July 15, 2014: European Journal of Pharmacology
K Deventer, K Roels, F T Delbeke, P Van Eenoo
This paper reviews the prevalence of legal and illegal stimulants in relation to doping-control analysis. Stimulants are among the oldest classes of doping agents, having been used since ancient times. Despite the ease with which they can be detected and the availability of sensitive detection methods, stimulants are still popular among athletes. Indeed, they remain one of the top three most popular classes of prohibited substances. Because the list of legal and illegal stimulants is extensive only a selection is discussed in detail...
August 2011: Analytical and Bioanalytical Chemistry
R Nageswara Rao, Pawan K Maurya, Dhananjay D Shinde
A rapid and reliable high-performance liquid chromatographic method for resolution of enantiomers of adrafinil [(±)-ADL], a novel vigilance promoting agent, and its synthetic intermediates was developed. The separation was carried out on a Chiralcel OJ-H using n-hexane-ethanol (62:38 v/v) as a mobile phase. The detection was carried out at 225 nm using a photodiode array (PDA) detector. The optical rotation and order of elution of enantiomers were assigned. The method is suitable not only for process development of ADL but also for quality assurance of bulk drugs and pharmaceuticals...
November 2010: Biomedical Chromatography: BMC
S Dubey, S Ahi, I M Reddy, T Kaur, A Beotra, S Jain
OBJECTIVE: Adrafinil and modafinil have received wide publicity and have become controversial in the sporting world when several athletes were discovered allegedly using these drugs as doping agents. By acknowledging the facts, the World Anti-Doping Agency (WADA) banned these drugs in sports since 2004. The present study explores the possibility of differentiating adrafinil and modafinil and their major metabolites under electron impact ionization in gas chromatograph-mass spectrometer (GC-MSD) and electrospray ionization in liquid chromatograph-mass spectrometer (LC-MS/MS) by studying the fragmentation pattern of these drugs...
December 2009: Indian Journal of Pharmacology
Ramisetti Nageswara Rao, Dhananjay D Shinde, Venna Ramesh, Ragampeta Srinivas
Modafinil, adrafinil and their related substances were synthesized and analyzed by RP-LC with ESI-MS/MS. The ionization mode, polarity, cone voltage, and chromatographic conditions were evaluated. The optimum LC-MS conditions to obtain fragment ions indispensable for identification of the structures were described. The bulk drugs purity of modafinil and adrafinil was evaluated on Kromasil C(18) column with ACN/0.02 M ammonium acetate as mobile phase in gradient elution mode at 30 degrees C. The method was found to be suitable not only for monitoring the reactions during the process development but also for quality assurance of modafinil and adrafinil...
May 2009: Journal of Separation Science
Jianghai Lu, Xiaobing Wang, Shuming Yang, Xin Liu, Yang Qin, Li Shen, Yun Wu, Youxuan Xu, Moutian Wu, Gangfeng Ouyang
A new and reliable two-step liquid chromatography/tandem mass spectrometry (LC/MS/MS) method in combination with gas chromatography/mass spectrometry (GC/MS) for the screening and confirmation of adrafinil and its major metabolites, modafinil and modafinil acid, in human urine has been developed and validated. The method involved reversed-phase C18 solid-phase extraction (SPE) cartridge extraction and MS analysis by means of LC/MS/MS and GC/MS. The study illustrated that the ESI capillary temperature played a key role in the formation of the protonated molecule...
June 2009: Rapid Communications in Mass Spectrometry: RCM
R Nageswara Rao, Dhananjay D Shinde
A simple and rapid normal-phase HPLC method for enantiospecific separation of a psychostimulant, adrafinil (ADL), and its metabolite modafinil (MDL) in rat serum and urine was developed. The separation was accomplished on a normal-phase polysaccharide stationary phase Chiralcel OJ-H using n-hexane-ethanol (62:38 v/v) as a mobile phase at a flow rate of 1.0 mL/min. Detection was carried out at 225 nm using a photo diode array (PDA) detector. The elution order of the enantiomers was determined by a polarimeter connected in series with the PDA...
August 2009: Biomedical Chromatography: BMC
R Nageswara Rao, Dhananjay D Shinde, M V N Kumar Talluri, Sachin B Agawane
A highly sensitive and specific liquid chromatography/tandem mass spectrometric (LC-MS/MS) method for investigating the pharmacokinetics of adrafinil in rats was developed. Rat serum pretreated by solid-phase extraction (SPE) was analyzed by LC-MS/MS with an electrospray ionization (ESI) interface. The mobile phase consisted of acetonitrile:water:acetic acid (35:65:0.1, v/v/v) in an isocratic elution mode pumped at 1.0 ml/min. The analytical column (250 mm x 4.6 mm i.d.) was packed with Kromasil C(18) material (5...
September 15, 2008: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
D Lagarde
Sports and military environments have many common features - intense physical activity, rigorous physical environment (heat, cold, high or low pressure, hypoxia, acceleration...), specific psychosocial atmosphere, team spirit. If combined with jet lag syndrome, these specific conditions can favor altered physical and mental performance. There is always the temptation to use drugs as a simple way to reduce the penalizing effects. The available compounds known to affect sleep and wakefulness include hypnotics, benzodiazepines and non benzodiazepines such as temazepam, zolopidem, and zopiclone, stimulants such as amphetamine and amphetamine-like agents, adrafinil, modafinil, caffeine and chronobiotics substances such as melatonin and, more recently, slow release caffeine...
July 2007: Annales Pharmaceutiques Françaises
Fabienne Massé, Martine Hascoët, Eric Dailly, Michel Bourin
RATIONALE: Selective serotonin reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors demonstrated an anxiolytic-like effect in the four-plate test (FPT). (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI; a 5-HT2A receptor agonist) also possessed strong anxiolytic-like effect in the same test. A 5-HT2A mechanism seems to be implicated in the mechanism of action of both antidepressants and DOI in this test. On the other hand, the alpha-adrenergic ligands have also demonstrated an activity in other models of anxiety...
January 2006: Psychopharmacology
Christa M Studzinski, Joseph A Araujo, Norton W Milgram
For the past 15 years we have investigated the aged beagle dog as a model for human aging and dementia. We have shown that dogs develop cognitive deficits and neuropathology seen in human aging and dementia. These similarities increase the likelihood that the model will be able to accurately predict the efficacy of Alzheimer's disease (AD) treatments as well as detect therapeutics with limited or no efficacy. Better predictive validity of cognitive-enhancing therapeutics (CETs) could lead to enormous cost savings by reducing the number of failed human clinical trials and also may reduce the likelihood of negative outcomes such as those recently observed in the AN-1792 clinical trials...
March 2005: Progress in Neuro-psychopharmacology & Biological Psychiatry
Stéphane Thobois, Jing Xie, Helena Mollion, Isabelle Benatru, Emmanuel Broussolle
We describe the first case of orofacial abnormal movements induced by adrafinil, a vigilance promoting agent of the same pharmacological class as modafinil. The dyskinesias did not spontaneously recover despite adrafinil withdrawal for a 4-month period. They were secondly dramatically improved by tetrabenazine, a presynaptic dopaminergic depleting drug which was introduced after the 4-month adrafinil-free period.
August 2004: Movement Disorders: Official Journal of the Movement Disorder Society
Christina T Siwak, P Dwight Tapp, Norton W Milgram
Previous studies in humans and dogs have reported beneficial effects of adrafinil on specific cognitive functions. The effects in dogs are limited to a single study examining discrimination learning. We wanted to further explore the cognitive effects of adrafinil in dogs. The purpose of the present study was to determine the effect of oral administration of adrafinil on visuospatial function in dogs. Eighteen aged beagle dogs were tested on a delayed nonmatching-to-position (DNMP) task 2 h following one of three possible treatments; 20 mg/kg of adrafinil, 10 mg/kg of adrafinil or a placebo control...
August 2003: Pharmacology, Biochemistry, and Behavior
C T Siwak, H Callahan, N W Milgram
1. Adrafmil is a novel vigilance promoting agent developed in France by Louis Lafon Laboratories. 2. Adrafinil causes increased locomotion without producing stereotypical activity in canines tested in an open field. 3. The effectiveness of a single treatment is long-lasting, and the effectiveness persists over repeated treatments. 4. Acquisition of a size discrimination problem is enhanced by adrafinil. This may be linked to performance motivation. 5. Adrafinil causes a long-lasting increase in high frequency electroencephalographic activity recorded from cortical electrodes...
July 2000: Progress in Neuro-psychopharmacology & Biological Psychiatry
C T Siwak, P Gruet, F Woehrlé, B A Muggenburg, H L Murphey, N W Milgram
OBJECTIVE: To compare the efficacy of adrafinil, propentofylline, and nicergoline for enhancing behavior of aged dogs. ANIMALS: 36 Beagles between 9 and 16 years old. PROCEDURE: Dogs were randomly assigned to receive adrafinil (20 mg/kg of body weight, PO, q 24 h; n = 12), propentofylline (5 mg/kg, PO, q 12 h; 12), or nicergoline (0.5 mg/kg, PO, q 24 h; 12) for 33 days. Baseline behaviors in an open field and in kennels (home cage) were recorded before treatment...
November 2000: American Journal of Veterinary Research
N W Milgram, C T Siwak, P Gruet, P Atkinson, F Woehrlé, H Callahan
Aged beagle dogs were trained on either a size or intensity discrimination task 2 h following treatment with either 20 mg/kg of adrafinil or a placebo control. Training continued until the dogs reached a predetermined criterion level of performance, or failed to acquire the task after 40 sessions. The treatments and tasks were then reversed, with both the test order and treatment order counterbalanced. Thus, half of the animals were first tested on the intensity discrimination, and half of these were first tested under adrafinil...
June 2000: Pharmacology, Biochemistry, and Behavior
C T Siwak, P Gruet, F Woehrlé, M Schneider, B A Muggenburg, H L Murphey, H Callahan, N W Milgram
Adrafinil, a vigilance enhancing pharmaceutical, was administered to aged dogs for 14 consecutive days at doses of 10, 20, 30, or 40 mg/kg using a crossover design. The effects on spontaneous behavior in a 10-min canine open-field test were systematically recorded every fourth day, starting with day 1 of treatment. The open field tests were given 2 or 10 h following oral administration of capsules containing either adrafinil or lactose, the placebo control. Adrafinil caused an increase in locomotor activity at the three highest doses at both the 2- and 10-h intervals and during both the first (days 1 and 5) and second treatment week (days 9 and 13)...
June 2000: Pharmacology, Biochemistry, and Behavior
F Grange, Y Scrivener, A Koessler, P Straub, J C Guillaume
BACKGROUND: Sporadic observations would suggest that certain drugs play a role in the development of pemphigoid. A recent case-control study on long-term drug use associated with pemphigoid was unable to confirm the suspected role of these drugs, but did demonstrate a significant association between the development of pemphigoid and use of spironolactone. CASE REPORT: An 82-year-old patient had bullous erythematous lesions on the left thigh suggestive of pemphigoid...
1997: Annales de Dermatologie et de Vénéréologie
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