Comprehensive analysis of prohibited substances and methods in sports: Unveiling trends, pharmacokinetics, and WADA evolution.

This review systematically compiles sports-related drugs, substances, and methodologies based on the most frequently detected findings from prohibited lists published annually by the World Anti-Doping Agency (WADA) between 2003 and 2021. Aligned with structure of the 2023 prohibited list, it covers all proscribed items and details the pharmacokinetics and pharmacodynamics of five representatives from each section. Notably, it explores significant metabolites and metabolic pathways associated with these substances. Adverse analytical findings are summarized in tables for clarity, and the prevalence is visually represented through charts. The review includes a concise historical overview of doping and WADA's role, examining modifications in the prohibited list for an understanding of evolving anti-doping measures.

Taurine in sports and exercise.

BACKGROUND: Taurine has become a popular supplement among athletes attempting to improve performance. While the effectiveness of taurine as an ergogenic aid remains controversial, this paper summarizes the current evidence regarding the efficacy of taurine in aerobic and anaerobic performance, metabolic stress, muscle soreness, and recovery. METHODS: Google Scholar, Web of Science, and MedLine (PubMed) searches were conducted through September 2020. Peer-reviewed studies that investigated taurine as a single ingredient at dosages of < 1 g - 6 g, ranging from 10 to 15 min-to-2 h prior to exercise bout or chronic dose (7 days- 8 weeks) of consumption were included. Articles were excluded if taurine was not the primary or only ingredient in a supplement or food source, not published in peer-reviewed journals, if participants were older than 50 years, articles published before 1999, animal studies, or included participants with health issues. A total of 19 studies met the inclusion criteria for the review. RESULTS: Key results include improvements in the following: VO2max, time to exhaustion (TTE; n = 5 articles), 3 or 4 km time-trial (n = 2 articles), anaerobic performance (n = 7 articles), muscle damage (n = 3 articles), peak power (n = 2 articles), recovery (n = 1 article). Taurine also caused a change in metabolites: decrease in lactate, creatine kinase, phosphorus, inflammatory markers, and improved glycolytic/fat oxidation markers (n = 5 articles). Taurine dosing appears to be effective at ~ 1-3 g/day acutely across a span of 6-15 days (1-3 h before an activity) which may improve aerobic performance (TTE), anaerobic performance (strength, power), recovery (DOMS), and a decrease in metabolic markers (creatine kinase, lactate, inorganic phosphate). CONCLUSIONS: Limited and varied findings prohibit definitive conclusions regarding the efficacy of taurine on aerobic and anaerobic performance and metabolic outcomes. There are mixed findings for the effect of taurine consumption on improving recovery from training bouts and/or mitigating muscle damage. The timing of taurine ingestion as well as the type of exercise protocol performed may contribute to the effectiveness of taurine as an ergogenic aid. More investigations are needed to better understand the potential effects of taurine supplementation on aerobic and anaerobic performance, muscle damage, metabolic stress, and recovery.

Is Individualization of Sodium Bicarbonate Ingestion Based on Time to Peak Necessary?

PURPOSE: To describe the reliability of blood bicarbonate pharmacokinetics in response to sodium bicarbonate (SB) supplementation across multiple occasions and assess, using putative thresholds, whether individual variation indicated a need for individualized ingestion timings. METHODS: Thirteen men (age 27 ± 5 yr; body mass [BM], 77.4 ± 10.5 kg; height, 1.75 ± 0.06 m) ingested 0.3 g·kg BM SB in gelatine capsules on three occasions. One hour after a standardized meal, venous blood was obtained before and every 10 min after ingestion for 3 h, then every 20 min for a further hour. Time to peak (Tmax), absolute peak (Cmax), absolute peak change ([INCREMENT]Cmax), and area under the curve were analyzed using mixed models, intraclass correlation coefficient, coefficient of variation and typical error. Individual variation in pharmacokinetic responses was assessed using Bayesian simulation with multilevel models with random intercepts. RESULTS: No significant differences between sessions were shown for blood bicarbonate regarding Cmax, [INCREMENT]Cmax or area under the curve (P > 0.05), although Tmax occurred earlier in SB2 (127 ± 36 min) than in SB1 (169 ± 54 min, P = 0.0088) and SB3 (159 ± 42 min, P = 0.05). Intraclass correlation coefficient, coefficient of variation, and typical error showed moderate to poor reliability. Bayesian modeling estimated that >80% of individuals from the population experience elevated blood bicarbonate levels above +5 mmol·L between 75 and 240 min after ingestion, and between 90 and 225 min above +6 mmol·L. CONCLUSIONS: Assessing SB supplementation using discrete values showed only moderate reliability at the group level, and poor reliability at the individual level, whereas Tmax was not reproducible. However, when analyzed as modeled curves, a 0.3-g·kg BM dose was shown to create a long-lasting window of ergogenic potential, challenging the notion that SB ingestion individualized to time-to-peak is a necessary strategy, at least when SB is ingested in capsules.

Glucocorticoids in elite sport: current status, controversies and innovative management strategies-a narrative review.

The use of systemic glucocorticoids (GCs), as well as local injections, continues to be a controversial issue in the sport/anti-doping community. There is widespread and legitimate use of GCs for numerous health conditions, yet there are concerns about side effects and the possibility of enhanced athletic performance in limited settings. This is compounded by the uncertainty regarding the prevalence of GC use, mechanisms underlying physiological effects and complex pharmacokinetics of different formulations. While WADA continues to promote research in this complex area, some international sporting federations, major event organisers and professional sports leagues have introduced innovative rules such as needle policies, mandatory rest periods and precompetition guidelines to promote judicious use of GCs, focusing on athlete health and supervision of medical personnel. These complementary sport-specific rules are helping to ensure the appropriate use of GCs in athletes where overuse is a particular concern. Where systemic GCs are medically necessary, Therapeutic Use Exemptions (TUEs) may be granted after careful evaluation by TUE Committees based on specific and strict criteria. Continued vigilance and cooperation between physicians, scientists and anti-doping organisations is essential to ensure that GC use in sport respects not only principles of fairness and adherence to the rules but also promotes athlete health and well-being. The purpose of this narrative review is to summarise the use and management of GCs in sport illustrating several innovative programmes by sport leagues and federations.

Fragmented Dosing of ß-alanine Induces A Body Weight-Independent Pharmacokinetic Response.

Personalised dosing of performance-enhancing food supplements is a hot topic. ß-alanine is currently dosed using a fixed dose; however, evidence suggests that this might favour light compared to heavy subjects. A weight-relative dose seems to reverse this problem. In the present study, a novel dosing strategy was tested. A fragmented dose, composed of a fixed fragment of 800 mg and a weight-relative fragment of 10 mg/kg body weight, was compared to a fixed dose of 1600 mg and a weight-relative dose of 20 mg/kg body weight in a cohort of 20 subjects with a body weight ranging 48-139 kg (79.9 ± 24.4 kg). The results show that, following a fragmented dose, the influence of body weight on the pharmacokinetic response (iAUC) over a 210 min period was absent (r = -0.168; p = 0.478), in contrast to the fixed or weight-relative dose. The pharmacokinetic response also seemed more homogenous (CV% = 26%) following a fragmented dose compared to the fixed (33%) and the weight-relative dose (31%). The primary advantage of the easy-to-calculate fragmented dosing strategy is that it does not systematically favour or impair a certain weight group. Thorough dosage studies are lacking in the current field of sports and food supplements, therefore similar considerations can be made towards other (ergogenic) food supplements.

Dietary guanidinoacetic acid does not accumulate in the brain of healthy men.

We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations. No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used.

Nicotine: Sporting Friend or Foe? A Review of Athlete Use, Performance Consequences and Other Considerations.

Nicotine use amongst athletes is high and increasing, especially in team sports. This narrative review examines the rationale behind its use and evidence of its effect on physical performance, and considers important factors that should determine future research efforts. To date, ten studies have assessed muscular strength and power, sub- or maximal endurance and high-intensity exercise when nicotine (medication) or smokeless tobacco was used as an intervention. Two studies observed an ergogenic effect, one an ergolytic with the remaining seven reporting no change. These studies have notable limitations and confounding factors that include participant tolerance to nicotine, interindividual responses, the nicotine delivery system used and failure to adhere to rigorous experimental/scientific design. Further research is encouraged to address these limitations and determine the extent to which anti-doping and governing bodies should consider promoting, coordinating and monitoring any effort against nicotine and nicotine-containing substances in sports.

Tyrosine Ingestion and Its Effects on Cognitive and Physical Performance in the Heat.

PURPOSE: Ingestion of tyrosine (TYR), a catecholamine precursor, has previously improved aspects of cognitive function and mood during acute stress, although there is limited research exploring the optimal dose relative to blood values. The serum responses of two doses of TYR were investigated (study 1), with the identified "optimal" dose assessed relative to cognitive and physical performance during a military-based protocol in the heat (study 2). METHODS: For study 1, 21 participants were assigned to one of the following three groups: HIGH (two doses of 150 mg · kg(-1) body mass TYR), LOW (two doses of 75 mg · kg(-1) body mass TYR), and CON (sugar-free drink). Participants ingested TYR in two separate doses (0900 and 1300 h) and remained in the laboratory from 0800 to 1700 h, having blood drawn every hour. For study 2, eight participants completed a military-based load carriage protocol composed of a 60-min walk (6.5 km · h(-1)) followed by a 2.4-km time trial carrying a 25-kg backpack (40°C; relative humidity, 30%) on two occasions (TYR/placebo) in a double-blind counterbalanced crossover design. Cognitive function was assessed before, during, and after exercise. RESULTS: Study 1 demonstrated that ingestion of a single dose of 150 mg · kg(-1) body mass TYR was equally efficient at elevating serum TYR concentration relative to a double dose. In study 2, exercise heat stress impaired some aspects of cognitive function; however, TYR did not alleviate these decrements (P > 0.05). Furthermore, no difference was observed in any physiological variable between conditions (P > 0.05) or time trial completion time (P = 0.74) between TYR (19.78 ± 3.44 min) and placebo (20.29 ± 3.55 min). CONCLUSIONS: Despite marked elevations in serum TYR concentration, ingestion of TYR did not influence cognitive function or physical performance during exercise heat stress.

Guanidinoacetic acid as a performance-enhancing agent.

Guanidinoacetic acid (GAA; also known as glycocyamine or guanidinoacetate) is the natural precursor of creatine, and under investigation as a novel dietary agent. It was first identified as a natural compound in humans ~80 years ago. In the 1950s, GAA's use as a therapeutic agent was explored, showing that supplemental GAA improved patient-reported outcomes and work capacity in clinical populations. Recently, a few studies have examined the safety and efficacy of GAA and suggest potential ergogenic benefits for physically active men and women. The purpose of this review is to examine possible applications of GAA supplementation for exercise performance enhancement, safety, and legislation issues.

Detection of testosterone esters in blood.

Injections of synthetic esters of testosterone are among the most common forms of testosterone application. In doping control, the detection of an intact ester of testosterone in blood gives unequivocal proof of the administration of exogenous testosterone. The aim of the current project was to investigate the detection window for injected testosterone esters as a mixed substance preparation and as a single substance preparation in serum and plasma. Furthermore, the suitability of different types of blood collection devices was evaluated. Collection tubes with stabilizing additives, as well as non-stabilized serum separation tubes, were tested. A clinical study with six participants was carried out, comprising a single intramuscular injection of either 1000 mg testosterone undecanoate (Nebido(®)) or a mixture of 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate, and 100 mg testosterone decanoate (Sustanon(®)). Blood was collected throughout a testing period of 60 days. The applied analytical method for blood analysis included liquid-liquid extraction and preparation of oxime derivatives, prior to TLX-sample clean-up and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection. All investigated testosterone esters could be detected in post-administration blood samples. The detection time depended on the type of ester administered. Furthermore, results from the study show that measured blood concentrations of especially short-chained testosterone esters are influenced by the type of blood collection device applied. The testosterone ester detection window, however, was comparable.

Determination of designer doping agent--2-ethylamino-1-phenylbutane--in dietary supplements and excretion study following single oral supplement dose.

The quantitative analysis of a new designer doping agent, 2-ethylamino-1-phenylbutane (EAPB) and its metabolite, 2-amino-1-phenylbutane (APB) in urine samples, and the determination of EAPB in dietary supplement samples, have been presented. The main purpose of the present study was to develop simple and reliable gas chromatography-mass spectrometry method (GC-MS) for excretion study following a single oral administration of dietary supplements containing EAPB. Three analytical methods for the determination of EAPB in urine and supplement samples, and APB in urine samples using the GC-MS system, have been validated. The method of the determination of EAPB in supplement samples was applied to analyze seventeen dietary supplements, CRAZE and DETONATE. Two other methods were used to determine the urinary excretion profile of EAPB and APB in the case of three healthy volunteers and, on further investigation, it was applied to the anti-doping control in sport. Quantification was obtained on the basis of the ions at m/z 86, 58 and 169, monitored for EAPB, APB and diphenylamine (used as an internal standard), respectively. The limits of detection and quantification were 2.4 and 7.3µg/g for EAPB in the case of supplement analysis, 2.9 and 8.8ng/mL for EAPB in the case of urine analysis, and 3.2 and 9.7ng/mL for APB. The other validation parameters as linearity, precision and trueness have been also investigated with the acceptable results. The extraction yield of all presented methods was above 69%. EAPB was detected in fourteen analyzed supplements (not included EAPB in their labels) and its content varied between 1.8 and 16.1mg/g. Following oral administration of three supplements with EAPB to one male and two female volunteers, the parent compound of EAPB and its metabolite were monitored and the excretion parameters as the maximum concentration of the analyte in urine (2.2-4.2µg/mL for EAPB; 1.1-5.1µg/mL for APB) and the time for the maximum height of the excretion peak (2-8h and 22h in one case for EAPB; 20-22h and 4h in one case for APB) have been indicated. EAPB and APB were detected at the level above 50ng/mL (50% of the minimum required performance level for stimulants in the anti-doping control in-competition in sport) in the urine up to 46-106h and 58-120h, respectively. Additionally, the result of the anti-doping control during swimming competition of one athlete, whose urine sample was analyzed for stimulants and narcotics, has been presented. The qualitative and quantitative analyses of new designer agents in urine samples and the excretion studies of these substances are of a great importance in the anti-doping control in sport. Moreover, the presentation of detection examples of these agents in supplements that haven't got included an information about them in the labeling, make athletes (and other supplement customers) more and more aware of the risk of the supplement use and possible health and doping consequences.

Annual banned-substance review: analytical approaches in human sports drug testing.

Within the mosaic display of international anti-doping efforts, analytical strategies based on up-to-date instrumentation as well as most recent information about physiology, pharmacology, metabolism, etc., of prohibited substances and methods of doping are indispensable. The continuous emergence of new chemical entities and the identification of arguably beneficial effects of established or even obsolete drugs on endurance, strength, and regeneration, necessitate frequent and adequate adaptations of sports drug testing procedures. These largely rely on exploiting new technologies, extending the substance coverage of existing test protocols, and generating new insights into metabolism, distribution, and elimination of compounds prohibited by the World Anti-Doping Agency (WADA). In reference of the content of the 2014 Prohibited List, literature concerning human sports drug testing that was published between October 2013 and September 2014 is summarized and reviewed in this annual banned-substance review, with particular emphasis on analytical approaches and their contribution to enhanced doping controls.

Smokeless tobacco, sport and the heart.

Smokeless tobacco (snuff) is a finely ground or shredded tobacco that is sniffed through the nose or placed between the cheek and gum. Chewing tobacco is used by putting a wad of tobacco inside the cheek. Smokeless tobacco is widely used by young athletes to enhance performance because nicotine improves some aspects of physiology. However, smokeless tobacco has harmful health effects, including cardiovascular disorders, linked to nicotine physiological effects, mainly through catecholamine release. Nicotine decreases heart rate variability and the ventricular fibrillation threshold, and promotes the occurrence of various arrhythmias; it also impairs endothelial-dependent vasodilation and could therefore promote premature atherogenesis. At rest, heart rate, blood pressure, inotropism, cardiac output and myocardial oxygen consumption are increased by nicotine, leading to an imbalance between myocardial oxygen demand and supply. The same occurs at submaximal levels of exercise. These increases are accompanied by a rise in systemic resistances. At maximal exercise, heart rate, cardiac output and maximal oxygen uptake (V˙O2max) are unaffected by nicotine. Because endothelial dysfunction is promoted by nicotine, paradoxical coronary vasoconstriction may occur during exercise and recovery. Nicotine induces a decrease in muscular strength and impairs anaerobic performance. However, nicotine is used in sports as it diminishes anxiety, enhances concentration and agility, improves aerobic performance and favours weight control. Importantly, smokeless tobacco, similar to cigarette smoking, leads to nicotine dependence through dopaminergic pathways. Smokeless tobacco has harmful cardiovascular effects and is addictive: it fulfils all the criteria for inclusion in the World Anti-Doping Agency prohibited list as a doping product. Smokeless tobacco use in sporting activities must be discouraged.

Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses.

Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses.

Detection and effects on serum and urine steroid and LH of repeated GnRH analog (leuprolide) stimulation.

Non-steroidal drugs that increase endogenous testosterone (T) may be used to exploit ergogenic effects of androgens in power sports. While superactive GnRH analog use is suspected, neither screening nor detection tests are developed. This study aimed to determine if (a) stimulation for 5 days by leuprolide (a superactive GnRH analog) of serum and urine steroids and urine LH is reproducible at a 2 week interval, (b) nandrolone decanoate (ND) co-administration masks responses to leuprolide administration, (c) performance of urine measurement of leuprolide and M1, its major metabolite, as a detection test. Healthy men were randomized into a 4 week parallel group, open label clinical study in which all men had daily sc injections of leuprolide (1mg) for 4 days in the 1st and 3rd weeks with hormone-free 2nd and 4th weeks. In the 3rd week, men were randomized to either ND injections or no extra treatment. Serum steroids were determined by liquid chromatography, tandem mass spectrometry (LC-MS), urine steroids by gas chromatography, mass spectrometry (GC-MS), urine leuprolide and M1 by high resolution LC-MS and urine LH by immunoassay. Leuprolide stimulated striking, reproducible increases in serum and urine LH and steroids (serum T, dihydroT (DHT), 3α diol; urine T, epitestosterone (E) and androsterone (A). ND suppressed basal serum T, E2, 3α diol, and urinary E but did not mask or change the magnitude of responses to leuprolide. Urine leuprolide and M1 measurement had 100% sensitivity and specificity in detecting leuprolide administration up to one day after cessation of injections with the detection window between 1 and 3 days after last dose. Screening using urine steroid and LH measurements, optimally by urinary log10(LHxT), correctly classified 82% of urine samples. It is concluded that leuprolide stimulation of endogenous testosterone is reproducible after a 10-day interval, is not masked by ND and is reliably detected by urine leuprolide or M1 measurement for at least 1 day after administration.

A new sulphate metabolite as a long-term marker of metandienone misuse.

Metandienone is one of the most frequently detected anabolic androgenic steroids in sports drug testing. Metandienone misuse is commonly detected by monitoring different metabolites excreted free or conjugated with glucuronic acid using gas chromatography mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) after hydrolysis with ß-glucuronidase and liquid-liquid extraction. It is known that several metabolites are the result of the formation of sulphate conjugates in C17, which are converted to their 17-epimers in urine. Therefore, sulphation is an important phase II metabolic pathway of metandienone that has not been comprehensively studied. The aim of this work was to evaluate the sulphate fraction of metandienone metabolism by LC-MS/MS. Seven sulphate metabolites were detected after the analysis of excretion study samples by applying different neutral loss scan, precursor ion scan and SRM methods. One of the metabolites (M1) was identified and characterised by GC-MS/MS and LC-MS/MS as 18-nor-17ß-hydroxymethyl-17α-methylandrost-1,4,13-triene-3-one sulphate. M1 could be detected up to 26 days after the administration of a single dose of metandienone (5 mg), thus improving the period in which the misuse can be reported with respect to the last long-term metandienone metabolite described (18-nor-17ß-hydroxymethyl-17α-methylandrost-1,4,13-triene-3-one excreted in the glucuronide fraction).

An electrochemical biosensor for clenbuterol detection and pharmacokinetics investigation.

Clenbuterol is a member of ß2 adrenergic agonists, which is widely used not only as a food additive for livestocks, but also a kind of stimulant for athletes; however, the abuse of clenbuterol may pose a significant negative impact on human health. Since it is highly required to develop fast, sensitive and cost-effective method to determine clenbuterol level in the suspected urine or blood, we herein have fabricated an electrochemical biosensor for the determination of clenbuterol. Measurement of the species with the proposed biosensor can also have the advantages of simplicity, high sensitivity and selectivity. Moreover, the sensor can be directly used for clenbuterol determination in rat urine. We have further studied the pharmacokinetics of clenbuterol by using this proposed electrochemical biosensor, so a new tool to investigate pharmacokinetic is developed in this work.

Pseudoephedrine and preexercise feeding: influence on performance.

PURPOSE: This study examined the influence of preexercise food intake on plasma pseudoephedrine (PSE) concentrations and subsequent high-intensity exercise. In addition, urinary PSE concentrations were measured under the same conditions and compared with the present threshold of the World Anti-Doping Agency (WADA). METHODS: Ten highly trained male cyclists and triathletes (age = 30.6 ± 6.6 yr, body mass [BM] = 72.9 ± 5.1 kg, and V˙O2max = 64.8 ± 4.5 mL·kg·min; mean ± SD) undertook four cycling time trials (TT), each requiring the completion of a set amount of work (7 kJ·kg BM) in the shortest possible time. Participants were randomized into a fed or nonfed condition and orally ingested 2.8 mg·kg BM of PSE or a placebo (PLA) 90 min before exercise; in the fed trials, they consumed a meal providing 1.5 g·kg BM of CHO. Venous blood was sampled at 30, 50, and 70 min and pre-warm-up and postexercise for the analysis of plasma PSE and catecholamine concentrations, and urine was also collected for the analysis of PSE concentration. RESULTS: Independent of the preexercise meal, 2.8 mg·kg BM of PSE did not significantly improve cycling TT performance. The fed trials resulted in lower plasma PSE concentrations at all time points compared with the nonfed trials. Both plasma epinephrine and blood lactate concentrations were higher in the PSE compared with the PLA trials, and preexercise and postexercise urinary PSE concentrations were significantly higher than the threshold (150 µg·mL) used by WADA to determine illicit PSE use. CONCLUSION: Irrespective of the preexercise meal, cycling TT performance of approximately 30 min was not improved after PSE supplementation. Furthermore, 2.8 mg·kg BM of PSE taken 90 min before exercise, with or without food, resulted in urinary PSE concentrations exceeding the present WADA threshold.

Nicotine facilitates memory consolidation in perceptual learning.

Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Formoterol concentrations in blood and urine: the World Anti-Doping Agency 2012 regulations.

INTRODUCTION: We examined urinary and serum concentrations of formoterol in asthmatic and healthy individuals after a single dose of 18 µg inhaled formoterol and after repeated inhaled doses in healthy individuals. Results were evaluated using the World Anti-Doping Agency (WADA) 2012 threshold for formoterol. METHODS: On the day of this open-label, crossover study, 10 asthmatic subjects who regularly used beta2-agonists and 10 healthy participants with no previous use of beta2-agonists received a single dose of 18 µg formoterol. Further, 10 nonasthmatic participants inhaled 18 µg formoterol every second hour until obtaining a total of 72 µg, which is twice the maximum daily dose (36 µg formoterol) permitted by the WADA. Blood samples were collected at baseline, 30 min, 1, 2, 3, 4, and 6 h after the first inhalation. Urine samples were collected at baseline, 0-4, 4-8, and 8-12 h after the first inhalation. RESULTS: Median urine concentration, corrected for specific gravity, after the single-dose administration peaked during 0-4 h after inhalation at a maximum of 7.4 ng·mL(-1) in asthmatic subjects and 7.9 ng·mL(-1) in healthy subjects. Median urine concentration after repeated doses peaked during 4-8 h after inhalation of a total of 72 µg formoterol at a maximum of 16.8 ng·mL(-1) in healthy participants. The maximum individual concentration of 25.6 ng·mL(-1) was found after inhalation of a total of 72 µg formoterol. CONCLUSIONS: We found no significant differences in urinary and serum concentrations of formoterol between asthmatic and healthy subjects. We found high interindividual variability in the concentrations in all groups. Our data support the WADA 2012 urinary threshold of 30 ng·mL(-1) formoterol as being an adverse analytical finding.