Sex attractant in a brown alga: chemical structure.

In the report "Sex attractant in a brown alga: Chemical structure" by D. G. Müller et al. [171, 815 (1971)], allo-cis-l-(cyclo-heptadien-2',5'-yl)-butene-1 in line 2 of the abstract and in line 4 of column 3, page 815 should read all-cis-l-(cycloheptadien-2',5'-yl)-butene-1.

Sex attractant in a brown alga: chemical structure.

The male-attracting substance produced by the female gametes of the marine brown alga Ectocarpus siliculosus was identified as allo-cis-1-(cycloheptadien-2',5'-yl)-butene-1.

Metabolism of metandienone in man: identification and synthesis of conjugated excreted urinary metabolites, determination of excretion rates and gas chromatographic-mass spectrometric identification of bis-hydroxylated metabolites.

After oral administration of metandienone (17 alpha-methyl-androsta-1,4-dien-17 beta-ol-3-one) to male volunteers conjugated metabolites are isolated from urine via XAD-2-adsorption, enzymatic hydrolysis and preparative high-performance liquid chromatography (HPLC). Four conjugated metabolites are identified by gas chromatography-mass spectrometry (GC/MS) with electron impact (EI)-ionization after derivatization with N-methyl-N-trimethyl-silyl-trifluoroacetamide/trimethylsilyl-imidazole (MSTFA/TMS-Imi) and comparison with synthesized reference compounds: 17 alpha-methyl-5 beta-androst-1-en-17 beta-ol-3-one (II), 17 alpha-methyl-5 beta-androst-1-ene-3 alpha,17 beta-diol (III), 17 beta-methyl-5 beta-androst-1-ene-3 alpha,17 alpha-diol (IV) and 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol (V). After administration of 40 mg of metandienone four bis-hydroxy-metabolites--6 beta,12-dihydroxy-metandienone (IX), 6 beta,16 beta-dihydroxy-metandienone (X), 6 beta,16 alpha-dihydroxy-metandienone (XI) and 6 beta,16 beta-dihydroxy-17-epimetandienone (XII)--were detected in the unconjugated fraction. The metabolites III, IV and V are excreted in a comparable amount to the unconjugated excreted metabolites 17-epimetandienone (VI), 6 beta-hydroxy-metandienone (VII) and 6 beta-hydroxy-17-epimetandienone (VIII). Whereas the unconjugated excreted metabolites show maximum excretion rates between 4 and 12 h after administration the conjugated metabolites III, IV and V are excreted with maximum rates between 12 and 34 h.

Gas chromatography/mass spectometry identification of long-term excreted metabolites of the anabolic steroid 4-chloro-1,2-dehydro-17alpha-methyltestosterone in humans.

The misuse of anabolic steroids by athletes has been banned by sports organizations and is controlled by the analysis of urine samples obtained from athletes using gas chromatography/mass spectrometry (GC/MS). To extend the retrospectivity of the analytical methods, research is focused on long-term excreted metabolites. Preliminary results concerning the long-term detection of metabolites of the anabolic androgenic steroid 4-chloro-1,2-dehydro-17alpha-methyltestosterone I are presented. A new metabolite 4-chloro-3alpha, 6 beta, 17beta-trihydroxy-17alpha-methyl-5beta-androst-l-en-16-one was isolated by high performance liquid chromatography (HPLC) from urine following a single oral administration of 40 mg of I and characterized. Metabolite II was excreted into urine with a maximum excretion rate at approximately 48 h after administration and could be detected by gas chromatography/high resolution mass spectrometry (GC/HRMS) for up to 14 days. Two further partly characterized metabolites III and IV were confirmed for more than 9 days. The same three metabolites, II-IV, in varying amounts were also detected in urine samples from athletes who administered I.

Urinary testosterone (T) to epitestosterone (E) ratios by GC/MS. I. Initial comparison of uncorrected T/E in six international laboratories.

Six laboratories in six countries collaborated to investigate the analytical method for estimating the testosterone to epitestosterone ratio (T/E) in urine by gas chromatography/mass spectrometry in the context of detecting the application of T as a doping agent in sport. The protocol specified many but not all details of reagents and instrument conditions. The design included the distribution and analysis of four urines with different T/E values, three replicates per value, and one standard. The ranges of mean T/E values for the four urines estimated by peak area (PA) were 0.32-0.42, 0.72-0.94, 0.91-1.14 and 3.19-5.48. The analyses of variance for these data and for the peak height (PH) data were significant for the laboratory factor (p < 0.0001). In addition there was a significant interaction between the urine factor and the laboratory factor which indicates the complexity of the analysis. T/E calculated using PA was not significantly different from that using PH. For within-laboratory precision all values for PH and PA were < 8.3%, and for between-laboratory precision all values were < 11.7% except for one (20.1%). The data represent a baseline for future experiments designed to elucidate the sources of within-and between-laboratory variance, and to harmonize estimates of T/E.

17-Epimerization of 17 alpha-methyl anabolic steroids in humans: metabolism and synthesis of 17 alpha-hydroxy-17 beta-methyl steroids.

The 17-epimers of the anabolic steroids bolasterone (I), 4-chlorodehydromethyltestosterone (II), fluoxymesterone (III), furazabol (IV), metandienone (V), mestanolone (VI), methyltestosterone (VII), methandriol (VIII), oxandrolone (IX), oxymesterone (X), oxymetholone (XI), stanozolol (XII), and the human metabolites 7 alpha,17 alpha-dimethyl-5 beta-androstane-3 alpha,17 beta-diol (XIII) (metabolite of I), 6 beta-hydroxymetandienone (XIV) (metabolite of V), 17 alpha-methyl-5 beta-androst-1-ene-3 alpha,17 beta-diol (XV) (metabolite of V), 3'-hydroxystanozolol (XVI) (metabolite of XII), as well as the reference substances 17 beta-hydroxy-17 alpha-methyl-5 beta-androstan-3-one (XVII), 17 beta-hydroxy-17 alpha-methyl-5 beta-androst-1-en-3-one (XVIII) (also a metabolite of V), the four isomers 17 alpha-methyl-5 alpha-androstane-3 alpha,17 beta-diol (XIX) (also a metabolite of VI, VII, and XI), 17 alpha-methyl-5 alpha-androstane-3 beta,17 beta-diol (XX), 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol (XXI) (also a metabolite of V, VII, and VIII), 17 alpha-methyl-5 beta-androstane-3 beta,17 beta-diol (XXII), and 17 beta-hydroxy-7 alpha,17 alpha-dimethyl-5 beta-androstan-3-one (XXIII) were synthesized via a 17 beta-sulfate that spontaneously hydrolyzed in water to several dehydration products, and to the 17 alpha-hydroxy-17 beta-methyl epimer. The 17 beta-sulfate was prepared by reaction of the 17 beta-hydroxy-17 alpha-methyl steroid with sulfur trioxide pyridine complex. The 17 beta-methyl epimers are eluted in gas chromatography as trimethylsilyl derivatives from a capillary SE-54 or OV-1 column 70-170 methylen units before the corresponding 17 alpha-methyl epimer. The electron impact mass spectra of the underivatized and trimethylsilylated epimers are in most cases identical and only for I, II, and V was a differentiation between the 17-epimers possible. 1H nuclear magnetic resonance (NMR) spectra show for the 17 beta-methyl epimer a chemical shift for the C-18 protons (singlet) of about 0.175 ppm (in deuterochloroform) to a lower field. 13C NMR spectra display differences for the 17-epimeric steroids in shielding effects for carbons 12-18 and 20. Excretion studies with I-XII with identification and quantification of 17-epimeric metabolites indicate that the extent of 17-epimerization depends on the A-ring structure and shows a great variation for the different 17 alpha-methyl anabolic steroids.

Metabolism of anabolic steroids in humans: synthesis of 6 beta-hydroxy metabolites of 4-chloro-1,2-dehydro-17 alpha-methyltestosterone, fluoxymesterone, and metandienone.

Hydroxylation at position 6 beta testosterone I (17 beta-hydroxyandrost-4-en-3-one) and the anabolic steroids 17 alpha-methyltestosterone II (17 beta-hydroxy-17 alpha-methylandrost-4-en-3-one), metandienone III (17 beta-hydroxy-17 alpha-methylandrosta-1,4-dien-3-one), 4-chloro-1,2-dehydro-17 alpha-methyltestosterone IV (4-chloro-17 beta-hydroxy-17 alpha-methylandrosta-1,4-dien-3-one), and fluoxymesterone V (9-fluoro-11 beta, 17 beta-dihydroxy-17 alpha-methylandrost-4-en-3-one) was achieved via light-induced autooxidation of the corresponding trimethysilyl 3,5-dienol ethers dissolved in isopropanol or ethanol. The reaction further yielded the 6 alpha-hydroxy isomer in low amounts. The 6 beta-hydroxy isomer of I-V and the 6 alpha-hydroxy isomers of I, III, and IV were isolated and characterized by 1H and 13C NMR, high-performance liquid chromatography, gas chromatography, and mass spectrometry. Human excretion studies with single administered doses of boldenone (17 beta-hydroxyandrosta-1,4-dien-3-one), 4-chloro-1,2-dehydro-17 alpha-methyltestosterone, fluoxymesterone, metandienone, 17 alpha-methyltestosterone, and [16,16,17-2H3] testosterone showed that 6 beta-hydroxylation is the major metabolic pathway in the metabolism of 4-chloro-1,2-dehydro-17 alpha-methyltestosterone, fluoxymesterone, and metandienone, whereas for boldenone, 17 alpha-methyltestosterone, and testosterone, 6 beta-hydroxylation is negligible.

Detection of dihydrotestosterone (DHT) doping: alterations in the steroid profile and reference ranges for DHT and its 5 alpha-metabolites.

Dihydrotestosterone (DHT), a biologically active metabolite of testosterone, may be misused in sports to benefit from its anabolic and psychotropic effects. After DHT application, a significant increase of the glucuronides of DHT and its metabolites can be expected for a certain time period depending upon dose, formulation, route of administration, and in case of percutaneous administration the chainlength of the ester. DHT and its metabolites can be monitored by gas-chromatography/mass spectrometry (GC/MS) after enzymatic hydrolysis and trimethylsilylation. To investigate the extent of the alteration of the urinary steroid profile after DHT application, timely controlled experiments have been performed with: a) oral application of [16,16,17-2H3]-DHT, and b) sublingual application of a 25 mg dose of DHT. In the experiment with [16,16,17-2H3]-DHT within 24 hours about 44% of the applied dose was recovered after hydrolysis with beta-glucuronidase from E. coli as di- or tri-deuterated 5 alpha-androstane glucuronides: androsterone (33.2%), 5 alpha-androsta-ne-3 alpha,17 beta-diol (2.5%), 5 alpha-androstane-3 beta, 17 beta-diol (0.9%), DHT (7.2%). Hydrolysis with beta-glucuronidase/arylsulfatase from Helix Pomatia resulted in a about 10% higher yield except for DHT. In the study with sublingual application of 25 mg of DHT the extent of the recovery of DHT and its metabolites was in the same range as for the deuterated DHT. The urinary glucuronide concentrations of DHT, androsterone (AND), 5 alpha-androstane-3 alpha, 17 beta-diol (5 alpha A3 alpha D) and 5 alpha-androstane-3 beta,17 beta-diol (5 alpha A3 beta D) and their ratios to etiocholanolone (ETIO), 5 beta-androstane-3 alpha, 17 beta-diol (5 beta A3 alpha D) and epitestosterone (EPIT) were increased for up to 48 hours after application. For doping control purposes concentrations of DHT, 5 alpha A3 alpha D, 5 alpha A3 beta D and ratios of 5 alpha-metabolites to non 5 alpha-metabolites such as DHT/ETIO, DHT/EPIT, 5 alpha A3 alpha D/5 beta A3 alpha D, 5 alpha A3 beta D/5 beta A3 alpha D, and AND/ETIO outside the reference ranges are a proof for DHT application. Reference ranges for Asian and Caucasian male and female athletes are calculated from data bases of the Asian Games 1994, the previous Asian Games 1990 and the routine doping control samples of Caucasian athletes measured in Cologne 1994. At the occasion of the 1994 Asian Games in Hiroshima alterations in the concentrations and ratios of the DHT depending parameters for outside there reference ranges have been found and have been sanctioned on this basis by the Medical Commission of the Organisation of Olympic Council of Asia (OCA).

The detection of doping agents in blood.

Gas chromatographic screening procedures have been evaluated which permit the detection of stimulants and sedatives in blood after administration of pharmacological doses. The techniques actually used in sample preparations and gas chromatographic work are presented as well as examples of pharmacokinetic studies and postive dope cases. The use of sensitive and selective detectors like the nigrogen-specific detector or a mass spectrometer is absolutely essential for routine work, as for non-specific detectors the number of "false positives" leads to an intolerable work load for the laboratory.

Metabolism of boldenone in man: gas chromatographic/mass spectrometric identification of urinary excreted metabolites and determination of excretion rates.

Urinary metabolites of boldenone (androsta-1,4-dien-17 beta-ol-3-one) following oral administration of boldenone (doses from 11 to 80 mg) to man were isolated from urine via XAD-2 adsorption and enzymatic hydrolysis with beta-glucuronidase from Escherichia coli. The isolated metabolites were derivatized with N-methyl-N-trimethylsilyltri- fluoroacetamide/trimethyliodosilane and analysed by gas chromatography/mass spectrometry with electron impact (EI) ionization at 70 eV. Boldenone (I) and four metabolites were identified after hydrolysis of the urine with beta-glucuronidase: 5 beta-androst-1-en-17 beta-ol-3-one (II), 5 beta-androst-1-ene-3 alpha, 17 beta-diol (III), 5 beta-androst-1-en-3 alpha-ol-17-one (IV) and 5 beta-androst-1-en-6 beta-ol-3,17-dione (V). Five further metabolites in low concentration were identified without enzymatic hydrolysis after treatment of the urine with potassium carbonate: 5 beta-androst-1-ene-3,17-dione (VI), 5 alpha-androst-1-ene-3,17-dione (VII), androsta-1,4-diene-3,17-dione (VIII), androsta-1,4-diene-6 beta,17 beta-diol-3-one (IX) and androsta-1,4-dien-6 beta-ol-3,17-dione (X). The identification of the metabolites is based on the gas chromatography retention index, high-performance liquid chromatography retention, EI mass spectrum, chemical reactions of the isolated metabolites, and synthesis of metabolites II, III, IV, VI and VII. The EI mass spectra of the bis-trimethylsilyl derivatives of boldenone and its metabolites display all intense molecular ions, M-15 ions and fragment ions originating from cleavage of the B-ring. The excreted metabolites can be separated in basic extractable labile conjugates and in stable conjugates. More than 95% of metabolites are excreted as stable conjugates.

Stereospecific Derivatization of Amphetamines, Phenol Alkylamines, and Hydroxyamines and Quantification of the Enantiomers by Capillary GC/MS.

The enantiomers of amphetamines, phenol alkylamines, and hydroxyamines are separated by using α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as the chiral derivatizing agent for amino groups. Prior to N-acylation, amine salts are converted into the free bases and hydroxyl groups into O-silyl ethers by reaction with N-methyl-N-silylamides. N-Methyl-N-(trimethylsilyl)trifluoroacetamide, N-methyl-N-(triethylsilyl)trifluoroacetamide, or N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide was used to protect the hydroxyl groups by TMS, TES, or the tBDMS groups. All these N-methyl-N-silylamides were able to convert amino salts to the free bases. The reaction is selective and rapid, and the diastereomeric derivatives are well separated by capillary gas-liquid chromatography. This procedure is suitable for simultaneous determination by gas chromatography/mass spectrometry with selected-ion monitoring and is also applicable to quantification of the compounds in a biological matrix.

Metabolism of stanozolol: identification and synthesis of urinary metabolites.

Urinary metabolites of stanozolol (17 alpha-methyl-17 beta-hydroxy-5 alpha-androst-2-eno(3,2-c)-pyrazole) following oral administration were isolated by chromatography on XAD-2 and by preparative high-performance liquid chromatography (HPLC) and identified by gas chromatography-mass spectrometry (GC/MS) with electron impact (EI)-ionisation. Stanozolol is excreted as a conjugate but is metabolized to a large extent. All identified metabolites are hydroxylated, namely at C-3' of the pyrazole ring and at C-4 beta, C-16 alpha and C-16 beta of the steroid. Less than 5% of the metabolites are found in the unconjugated urine fraction: 3'-hydroxy-stanozolol (II) and 3'-hydroxy-17-epistanozolol (III). Conjugated excreted metabolites are 3'-hydroxystanozolol (II), stanozolol (I), 4 beta-hydroxy-stanozolol (IV), 16 beta-hydroxystanozolol (V), 16 alpha-hydroxystanozolol (VI), two isomers of 3',16-dihydroxystanozolol (VII, VIII), two isomers of 4 beta, 16-dihydroxystanozolol (IX, X) and a 3',?-dihydroxystanozolol (XI). 3'-Hydroxystanozolol, 4 alpha-hydroxystanozolol, 4 beta-hydroxystanozolol, 16 alpha-hydroxy-, 16 alpha-hydroxy-17-epi- and 16 beta-hydroxystanozolol were synthesised to confirm the structural assignment of the main metabolites.

[Determination of indolalkylamines after selective derivatisation (author's transl)]. / Nachweis von Indolalkylaminen nach selektiver Derivatisierung

The 1N-TMS-omegan-TFA-derivatives of indolalkylamines are suitable for estimation by combined gas chromatography and mass spectrometry for two reasons, viz. (1) Under electron impact charge stabilisation at the indole nucleus is favoured, so structure-specific ions form the base peak. For unsubstituted indoles m/e values of 202 are found and for hydroxyl-substituted indoles m/e values of 290. (2) The calibration curves of the derivatives are linear, even in the femtomole range. The 1N-TMS-omegan-derivatives can easily be obtained by trimethylsilylation with N-methyl-N-trimethylsilyltrifluoroacetamide containing catalytic amounts of N-trimethylsilylimidazole followed by acylation with N-methyl bis(trifluoroacetamide). The serotonin concentrations in different rat tissues are determined by this method of selective omegaN-trifluoroacylation-1N-trimethylsilylation and compared with the values obtained by pertrimethylsilylation.

Testosterone application influences sympathetic activity of intracardiac nerves in non-trained and trained mice.

Application of testosterone and/or physical exercise causes degenerative and then regenerative patterns of intracardiac sympathetic neurons. Observations in 3 stages (1, 3 and 6 weeks) illustrate the adaptative changes of sympathetic neurons as a response to these stimuli and show that the effects following testosterone application or physical exercise are comparable. Ultrastructural investigations indicate that the sympathetic neurons are more sensitive to testosterone than to physical exercise. The combination of testosterone plus training indicates overlapping effects of these two stimuli. The system of adrenergic nerve fibers seems to be overstimulated. Its reaction pattern is found not only to depend on time but also on the intensity of the stimuli.

[Metabolism and pharmacokinetics of etofylline clofibrate, new antilipemic]. / Metabolismus und Pharmakokinetik von Etofyllinclofibrat, einem neuen Antilipmikum.

Upon investigations on metabolism and pharmacokinetics of 1-(theophyllin-7-yl)-ethyl-2-[2-(chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, ML 1024, Duolip) is reported. As can be seen from in vivo tests in rats and dogs ML 1024 is cleaved to the metabolites clofibric acid and etofylline. This could be further demonstrated in vitro by incubation with lipases and human serum. The pharmacokinetic parameters of the metabolites after oral application of 2 capsules Duolip, corresponding to 500 mg etofylline clofibrate, were evaluated in 7 healthy volunteers. The serum fluctuations of the main metabolites could be adapted to an open two-compartment model (etofylline). The following mean values were found: the invasion half-life is 1 h 4 min for clofibric acid and 1 h 52 min for etofylline. The maximum concentration after approximately 4 h is 22.75 micrograms/ml for clofibric acid and 6.57 micrograms/ml for etofylline. The elimination half-life is 12.12 h for clofibric and 4.33 h for etofylline. Via urine 20 mg clofibric acid and 15.7 mg etofylline were excreted within 8 h. The elimination process after 8 h is not yet terminated.

Effect of O2 availability on neuroendocrine variables at rest and during exercise: O2 breathing increases plasma prolactin.

Neuroendrocrine and substrate responses were investigated in eight male athletes during inhalation of either 100% O2 (HE), 14% O2 (HO) or normoxio gas (NO) before, during and after 60 min of cycle ergometry at the same absolute work rate. Concentrations of prolactin (PRL), growth hormone (GH), testosterone (T), adrenocorticotropic hormone (ACTH), cortisol (COR), adrenalin (A), noradrenalin (NA), insulin (INS), ammonia (NH3), free fatty acids, serotonin (5-HT), total protein, branched-chain amino acids (BCAA) and free tryptophan (free TRP) were determined in venous blood and lactate concentration [LA-], partial pressure of oxygen (PO2), oxygen saturation (SO2), partial pressure of carbon dioxide and pH in capillary blood. The PO2 and SO2 were augmented in HE and decreased in HO (P < or = 0.01). In HO and NO no significant changes were found for any other parameter during 30 min of rest prior to exercise. In HE, PRL increased by about 400% during this time, while NA declined (P < or = 0.01). Heart rate (HR) and [LA-] were higher during exercise in HO (P < or = 0.01). In all trials, NH3, NA, A, T, GH and ACTH increased during exercise (P < or = 0.01), while BCAA and INS declined. In comparison to NO and HE, increases of NA, A, GH, COR and ACTH were higher in HO (P < or = 0.01). The PRL in NO and COR in NO and HE did not change significantly. In HE, after the initial increase at rest, PRL declined during exercise but remained higher than in HO. Higher values for NA, A, GH, COR and ACTH in HO were likely to have reflected an augmented relative exercise intensity. Our results showed that PRL but no other hormone increased during acute exposure to hyperoxia. This PRL release was independent of exercise stress and greater than PRL augmentation during hypoxia, which was related to a higher relative exercise intensity as indicated by [LA-] and HR. Responses of plasma NH3, BCAA, free TRP and 5-HT could not explain PRL augmentation induced by the increment in blood SO2 during hyperoxia.

Excretion of norephedrine by man after oral administration of oxyfedrine.

After oral administration of oxyfedrine to healthy volunteers, norephedrine was identified in the urine by thin layer chromatography and gas liquid chromatography and mass spectrography. 30 hours after single oral doses of 8, 16 or 24 mg of oxyfedrine, about 4, 8 and 9 mg, respectively, of norephedrine were found in the urine, i.e. on a molar base 75-100% of the dose was excreted as norephedrine. The peak of excretion occurred within 2-4 hours after administration of the drug. No accumulation of oxyfedrine and/or its metabolite was observed after administration of 16 mg of oxyfedrine t.i.d. for three days. It could not be decided whether oxyfedrine was metabolized to norephedrine by liver enzymes, as in rats, or was spontaneously degraded to norephedrine, e.g. in duodenal fluid before absorption. 30-150 min after oral oxyfedrine (24 mg) norephedrine was demonstrable in duodenal fluid. Thus, in addition to the direct beta-sympathomimetic effects of oxyfedrine, it may also have indirect sympathomimetic effects because of the noradrenaline-releasing properties of its metabolite norephedrine.

Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans.

Effects of a serotonin re-uptake inhibitor and oral amino acid supplementations on physical and mental performance as well as neuroendocrine variables were investigated. 10 male subjects cycled in four trials until exhaustion. Participants ingested a placebo in trial (T) I, 20 mg paroxetine in T II, 21 g branched-chain amino acids (BCAA) in T III and 20g tyrosine (TYR) in T IV. Heart rate, capillary lactate, plasma insulin, free fatty acids, glucose, serotonin and beta-endorphin did not differ in trials. Plasma ammonia increments during exercise were higher in T III. Plasma BCAA in T III and plasma TYR in T IV were increased after 30 min of exercise according to the supplemented substances. In contrast to all other trials, the ratio of plasma free TRP/BCAA did not increase in T III. Plasma TYR/BCAA was augmented in T IV and decreased in T III after 30 min of exercise, whereas it did not change in T I and II. Plasma prolactin (PRL), growth hormone, cortisol, adrenocorticotropic hormone, norepinephrine and epinephrine increased during all trials. Plasma PRL increments were higher in T IV. Exhaustion was reached earlier in T II. No significant differences were found between other trials. Drive during psychometric testing subsequent to exercise was improved in T III and IV. The results indicate that fatigue during endurance exercise was increased by pharmacological augmentation of the brain serotonergic activity. However, a reduction of 5-HT synthesis via BCAA supplementation did not affect physical fatigue. TYR administration did not alter physical performance either although plasma PRL increments suggest that changes in the monoaminergic system were induced. Precaution is necessary before assuming an ergogenic value of amino acids.