RESUMO
BACKGROUND: Weight loss and sports supplements containing deterenol have been associated with serious adverse events including cardiac arrest. OBJECTIVE: To determine the presence and quantity of experimental stimulants in dietary supplements labeled as containing deterenol sold in the United States. METHODS: Dietary supplements available for sale in the US and labeled as containing deterenol or one of its synonyms (e.g., isopropylnorsynephrine and isopropyloctopamine) were purchased online. For each brand, one container or subsample was analyzed by NSF International (Ann Arbor, MI) and one container or subsample by the Netherland's National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands). When differences existed between the two containers or subsamples of the same brand, both products were reanalyzed by Sciensano (Brussels, Belgium). NSF International carried out qualitative and quantitative analyses using ultra-high-performance liquid chromatography (UHPLC) quadrupole-Orbitrap mass spectrometry. RIVM performed qualitative and quantitative analysis using UHPLC quadrupole time-of-flight mass spectrometry. Sciensano carried out qualitative analysis using UHPLC quadrupole-Orbitrap mass spectrometry. RESULTS: Seventeen brands of supplements were analyzed. Many brands included more than one prohibited stimulant in the same product: 4 brands (24%, 4/17) included 2 stimulants, 2 (12%, 2/17) combined 3 stimulants, and 2 (12%, 2/17) combined 4 stimulants. The range of quantities per recommended serving size of the 9 stimulants detected were 2.7 mg to 17 mg of deterenol; 1.3 mg to 20 mg of phenpromethamine (Vonedrine); 5.7 mg to 92 mg of beta-methylphenylethylamine (BMPEA); 18 mg to 73 mg of octodrine; 18 mg to 55 mg of oxilofrine; 48 mg of higenamine; 17 mg of 1,3-dimethylamylamine (1,3-DMAA); 1.8 mg to 6.6 mg of 1,3-dimethylbutylamine (1,3-DMBA); and 5.3 mg of 1,4-dimethylamylamine (1,4-DMAA). CONCLUSION: Weight loss and sports supplements listing deterenol as an ingredient contained 9 prohibited stimulants and 8 different mixtures of stimulants, with as many as 4 experimental stimulants per product. These cocktails of stimulants have never been tested in humans and their safety is unknown.
Assuntos
Agonistas Adrenérgicos/análise , Fármacos Antiobesidade/análise , Estimulantes do Sistema Nervoso Central/análise , Suplementos Nutricionais/análise , Agonistas Adrenérgicos/efeitos adversos , Alcaloides/análise , Aminas/análise , Anfetaminas/análise , Fármacos Antiobesidade/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Qualidade de Produtos para o Consumidor , Suplementos Nutricionais/efeitos adversos , Efedrina/análogos & derivados , Efedrina/análise , Heptanos/análise , Humanos , Octopamina/análogos & derivados , Octopamina/análise , Medição de Risco , Tetra-Hidroisoquinolinas/análise , Estados UnidosRESUMO
In our searching for novel tyrosinase inhibitors from natural sources, (S)-N-trans-feruloyloctopamine isolated from garlic skin was found to be a potential mushroom tyrosinase inhibitor. Here, we examined the effects of the potential tyrosinase inhibitor in B16F10 cells on intracellular melanin contents, cytotoxicity, and the signaling mechanism involved in the expression of tyrosinase. The results showed the inhibitor displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin contents in a dose-dependent manner in the α-MSH-stimulated B16F10 cells. Real-time PCR and Western blot analysis showed that it inhibits melanogenesis signaling by down-regulates mRNA and protein expression levels of tyrosinase, which leads to a lower melanin contents. These results suggested that (S)-N-trans-feruloyloctopamine was an ideal tyrosinase inhibitor, and could be used in food and medical industry.
Assuntos
Ácidos Cumáricos/farmacologia , Inibidores Enzimáticos/farmacologia , Alho/química , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Melaninas/metabolismo , Melanoma/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/genética , Octopamina/análogos & derivados , Agaricales/enzimologia , Animais , Linhagem Celular Tumoral , Ácidos Cumáricos/química , Ácidos Cumáricos/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Melanoma/patologia , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Octopamina/química , Octopamina/isolamento & purificação , Octopamina/farmacologia , Relação Estrutura-AtividadeRESUMO
Hepatic oxidative stress plays a key role in the development of non-alcoholic steatohepatitis (NASH), therefore, treatment approaches that address the antioxidant is helpful in the therapy of patients with NASH. N-trans-coumaroyloctopamine (1) and N-trans-feruloyloctopamine (2) were identified as the primary antioxidant constituents of garlic skin with high antioxidant activities. The aim of this study was to elucidate the protective effect and mechanism of the antioxidants on NASH in rats. The results provide morphological and molecular biological evidences for the protective role of the antioxidant 2 in ameliorating oxidative stress and hepatic apoptosis in experimental NASH for the first time. Mechanism study indicated that the antioxidant 2 significantly reduced the expression of COX-2 mRNA and protein by western blot, RT-PCR and immunohistochemical techniques.
Assuntos
Antioxidantes/farmacologia , Alho/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Estrutura Molecular , Octopamina/análogos & derivados , Octopamina/farmacologia , Ratos Sprague-DawleyRESUMO
The aim of our report is to increase awareness that the antioxidant alpha-lipoic acid, which is marketed primarily as weight loss and energy supplement, has potentially lethal effects. A 14-year-old girl ingested in suicidal intention a large amount of alpha-lipoic acid, which led to multiorgan failure and subsequent death within 24 h. Multiorgan failure consisted of decreased myocardial contractility, seizures, anuria, thrombocytopenia, and coagulopathy. Therapy consisted of ventilation, anticonvulsive treatment and circulatory support with high-dose catecholamines. According to alpha-lipoic acid serum levels following ingestion the girl must have ingested a minimum of 10 alpha-lipoic acid tablets of 600 mg each. This is the first report on a fatal case of alpha-lipoic acid ingestion, which is intended to inform physicians, pharmacists and patients about critical side effects of this allegedly innocuous drug.
Assuntos
Fármacos Antiobesidade/intoxicação , Antioxidantes/intoxicação , Overdose de Drogas/terapia , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Tentativa de Suicídio , Ácido Tióctico/intoxicação , Acetaminofen/intoxicação , Adolescente , Cuidados Críticos , Overdose de Drogas/diagnóstico , Evolução Fatal , Feminino , Humanos , Insuficiência de Múltiplos Órgãos/terapia , Octopamina/análogos & derivados , Octopamina/intoxicaçãoRESUMO
The weight loss observed in consumers of extracts of Citrus aurantium (bitter orange) has been tentatively attributed to the lipolytic and thermogenic effects of the alkaloids abundant in the unripe fruit. Synephrine, octopamine, tyramine, and other alkaloids have been repeatedly identified and quantified in Citrus members of the Rutaceae family or in their extracts incorporated in dietary supplements for weight management. However, there are only scarce reports on their lipolytic action. This study aimed at comparing the acute lipolytic activity of synephrine, octopamine, tyramine, and N-methyltyramine in rat and human adipocytes. Maximal response to the prototypical ß-adrenergic agonist isoprenaline was taken as reference in both species. In rat, octopamine was slightly more active than synephrine while tyramine and N-methyl tyramine did not stimulate-and even inhibited-lipolysis. In human adipocytes, none of these amines stimulated lipolysis when tested up to 10 µg/ml. At higher doses (≥100 µg/ml), tyramine and N-methyl tyramine induced only 20% of the maximal lipolysis and exhibited antilipolytic properties. Synephrine and octopamine were partially stimulatory at high doses. Since synephrine is more abundant than octopamine in C. aurantium, it should be the main responsible for the putative lipolytic action of the extracts claimed to mitigate obesity. Noteworthy, their common isopropyl derivative, isopropylnorsynephrine (also named isopropyloctopamine or betaphrine), was clearly lipolytic: active at 1 µg/ml and reproducing more than 60% of isoprenaline maximal effect in human adipocytes. This compound, not detected in C. aurantium, and which has few reported adverse effects to date, might be useful for in vivo triglyceride breakdown.
Assuntos
Adipócitos Brancos/efeitos dos fármacos , Citrus/química , Lipólise/efeitos dos fármacos , Lipotrópicos/farmacologia , Octopamina/análogos & derivados , Extratos Vegetais/farmacologia , Sinefrina/farmacologia , Adipócitos Brancos/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Epinefrina/farmacologia , Feminino , Glucose/metabolismo , Humanos , Isoproterenol/farmacologia , Monoaminoxidase/metabolismo , Octopamina/química , Octopamina/farmacologia , Oxirredução , Ratos , Ratos Wistar , Tiramina/análogos & derivados , Tiramina/farmacologiaRESUMO
Potato plants ( SOLANUM TUBEROSUM L. cv. Indira) were grown at two levels of N supply in the greenhouse. Plants supplied with 0.8 g N per plant (high N variant) showed significantly increased biomass as compared to plants without additional N fertilisation (low N variant). C/N ratio was lower and protein content was higher in leaves of the high N variant. The concentration of chlorogenic acids and flavonols was significantly lower in leaves from the high N variant. Whereas resistance to ALTERNARIA SOLANI increased when plants were supplied with additional nitrogen, these plants were more susceptible to PHYTOPHTHORA INFESTANS. After infection with both pathogens, we found a strong induction of p-coumaroylnoradrenaline and p-coumaroyloctopamine, which are identified for the first time in potato leaves and are discussed as resistance factors of other solanaceous plants.
Assuntos
Alternaria/fisiologia , Nitrogênio/farmacologia , Phytophthora/fisiologia , Solanum tuberosum/metabolismo , Solanum tuberosum/microbiologia , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Fertilizantes , Estrutura Molecular , Norepinefrina/análogos & derivados , Norepinefrina/química , Norepinefrina/metabolismo , Octopamina/análogos & derivados , Octopamina/química , Octopamina/metabolismo , Fenóis/metabolismo , Doenças das Plantas/microbiologia , Solanum tuberosum/efeitos dos fármacos , Fatores de TempoRESUMO
Four phenolic amides, dihydro-N-caffeoyltyramine (1), trans-N-feruloyloctopamine (2), trans-N -caffeoyltyramine (3), and cis-N-caffeoyltyramine (4), were isolated from an ethyl acetate extract of the root bark of Lycium chinense Miller. All had an anti-fungal effect; compounds 1-3 were potent at 5-10 microg ml(-1) and were without hemolytic activity against human erythrocyte cells. Compound 4 was active at 40 microg ml(-1). All four compounds impeded the dimorphic transition of pathogen, Candida albicans.
Assuntos
Amidas/farmacologia , Antifúngicos/farmacologia , Ácidos Cafeicos/farmacologia , Ácidos Cumáricos/farmacologia , Lycium/metabolismo , Octopamina/análogos & derivados , Octopamina/farmacologia , Casca de Planta/metabolismo , Extratos Vegetais , Tiramina/análogos & derivados , Tiramina/farmacologia , Biotecnologia , Ácidos Cafeicos/química , Candida albicans/metabolismo , Ácidos Cumáricos/química , Eritrócitos/efeitos dos fármacos , Hemólise , Humanos , Espectroscopia de Ressonância Magnética , Modelos Químicos , Octopamina/química , Saccharomyces cerevisiae/metabolismo , Trichosporon/metabolismo , Tiramina/químicaRESUMO
The metabolic flux of two phenylpropanoid metabolites, N-p-coumaroyloctopamine (p-CO) and chlorogenic acid (CGA), in the wound-healing potato tuber tissue was quantitatively analyzed by a newly developed method based upon the tracer experiment using stable isotope-labeled compounds and LC-MS. Tuber disks were treated with aqueous solution of L-phenyl-d(5)-alanine, and the change in the ratio of stable isotope-labeled compound to non-labeled (isotope abundance) was monitored for p-CO and CGA in the tissue extract by LC-MS. The time-dependent change in the isotope abundance of each metabolite was fitted to an equation that was derived from the formation and conversion kinetics of each compound. Good correlations were obtained between the observed and calculated isotope abundances for both p-CO and CGA. The rates of p-CO formation and conversion (i.e. fluxes) were 1.15 and 0.96 nmol (g FW)(-1) h(-1), respectively, and for CGA, the rates 4.63 and 0.42 nmol (g FW)(-1) h(-1), respectively. This analysis enabled a direct comparison of the biosynthetic activity between these two compounds.
Assuntos
Ácido Clorogênico/metabolismo , Octopamina/análogos & derivados , Octopamina/biossíntese , Caules de Planta/metabolismo , Propanóis/metabolismo , Solanum tuberosum/metabolismo , Algoritmos , Cromatografia Líquida , Ácidos Cumáricos/metabolismo , Marcação por Isótopo/métodos , Espectrometria de Massas , Modelos Biológicos , Fenilalanina/farmacologia , Caules de Planta/efeitos dos fármacos , Traçadores Radioativos , Solanum tuberosum/efeitos dos fármacos , Estresse MecânicoRESUMO
Treatment of potato tuber tissues with beta-1,3-glucooligosaccharide induces accumulation of (S)-N-p-coumaroyloctopamine (p-CO). We examined the role of reactive oxygen species (ROS) and nitric oxide (NO) in the signal transduction leading to p-CO accumulation. Induction was suppressed by an NADPH-oxidase inhibitor, diphenyleneiodonium chloride, and oxygen radical scavengers. H2O2 was generated in the tuber tissue within a few minutes of treatment with beta-1,3-glucooligosaccharide. On the other hand, treatment with NO specific scavenger, nitric oxide synthase inhibitor, and serine protease inhibitor did not inhibit p-CO induction. Our findings suggest that ROS generated by the action of NADPH-oxidase play an important role in this system, while NO and serine protease are unlikely to be involved in this process.
Assuntos
Ácidos Cumáricos/metabolismo , Octopamina/análogos & derivados , Octopamina/metabolismo , Oligossacarídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Solanum tuberosum/metabolismo , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Inibidores Enzimáticos/farmacologia , Glucanos , Glucose , Peróxido de Hidrogênio/metabolismo , NADPH Oxidases/metabolismo , Oniocompostos/farmacologia , Fenilalanina Amônia-Liase/metabolismo , Polissacarídeos/farmacologia , Transdução de Sinais , Solanum tuberosum/efeitos dos fármacos , Tirosina Descarboxilase/metabolismoRESUMO
Potato tuber disks, when treated with laminarin, a beta-1,3-glucooligosaccharide from Laminaria digitata, accumulate a hydroxycinnamoyl amide compound, N-p-coumaroyloctopamine (p-CO). The biosynthesis of p-CO was investigated by feeding experiments, in order to show that the precursors of N-p-coumaroyl and octopamine moieties of p-CO are L-phenylalanine and L-tyrosine, respectively. The treatment of potato tuber tissue with laminarin resulted in elevated activities of four enzymes which are putatively involved in p-CO biosynthesis: phenylalanine ammonia lyase (PAL; EC 4.3.1.5), 4-hydroxycinnamic acid:CoA ligase (4CL; EC 6.2.1.12), hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110) and tyrosine decarboxylase (TyrDC; EC 4.1.1.25). Among these, the response of TyrDC was specific to laminarin treatment, thus indicating that the regulation of TyrDC activity is critical for the accumulation of p-CO in potato tuber tissue.
Assuntos
Ácidos Cumáricos/metabolismo , Octopamina/análogos & derivados , Polissacarídeos/farmacologia , Solanum tuberosum/enzimologia , Aciltransferases/metabolismo , Coenzima A Ligases/metabolismo , Ativação Enzimática , Glucanos , Cinética , Octopamina/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Raízes de Plantas/enzimologia , Tirosina Descarboxilase/metabolismoRESUMO
Treatment of potato tuber tissue with beta-1,3-oligoglucosaccharide causes an accumulation of N-p-coumaroyloctopamine (1). In order to determine the absolute structure of 1 in potato, optically active 1 was synthesized from (R)-octopamine which had been obtained from the racemic mixture by the fractional crystallization. By comparing the chromatographic behavior of synthetic and naturally-occurring samples with a chiral HPLC analysis, the absolute configuration of 1 in potato was determined to be S. This indicates that the absolute configuration of the octopamine moiety of 1 is opposite to that of octopamine formed in animal tissues.
Assuntos
Ácidos Cumáricos/química , Octopamina/análogos & derivados , Octopamina/química , Solanum tuberosum/química , Estrutura Molecular , OligossacarídeosRESUMO
The stereoselective accumulation of alpha-methyl-p-tyramine (AMPT) and alpha-methyl-p-octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)- and (-)-isomers of amphetamine (Amphet) and the acute administration of (+)- and (-)-AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Two h after the administration of (+)- or (-)-AMPT (5 mg kg-1 i.p.), the concentrations of the isomers in striatal tissue were approximately equal; 18 h later, the concentration of the (+)-isomer was 10 times that of the (-)-isomer. The concentrations of AMPO in the striatum and hypothalamus 20 h after administration of (+)-AMPT were 68 ng g-1 and 484 ng g-1 respectively. After the administration of the (-)-isomer of AMPT, small quantities of AMPO were detected in both brain areas. Twenty h after the last of 7 daily injections of (+)-Amphet (5 mg kg-1, i.p.), the concentration of AMPO in the hypothalamus was 5.4 times the concentration at 20 h after one injection. In the striatum, the corresponding ratio for AMPO was 3.5 and for AMPT was 2.5. These data indicate that, although both isomers of AMPT formed from Amphet administered systemically, cross the blood brain barrier, the (+)-isomers AMPT and AMPO are preferentially stored in striatal and hypothalamic aminergic nerve terminals. The accumulations of AMPT and AMPO in rat striatum and hypothalamus after chronic administration of Amphet demonstrates that these metabolites persist in neuronal storage in these brain areas for days after administration. The half-lives of (+)-AMPT and (+)-AMPO in striatal neuronal storage, calculated from this data, were 1.5 days and 2.5 days, respectively. The corresponding half-life for hypothalamic (+)-AMPO was 7 days. 7. These findings suggest the involvement of accumulated AMPT and AMPO in the development of behavioural augmentation to repeated injections of Amphet (Randrup & Munkvad, 1970).
Assuntos
Anfetamina/metabolismo , Compostos de Benzil/metabolismo , Corpo Estriado/metabolismo , Hipotálamo/metabolismo , Octopamina/análogos & derivados , Tiramina/análogos & derivados , Anfetamina/farmacologia , Animais , Meia-Vida , Hidroxilação , Masculino , Ratos , Estereoisomerismo , Tiramina/metabolismo , Tiramina/farmacologiaRESUMO
A simple method for screening drugs that influence tracheobronchial secretion has been described. After i.p. application of a phenol red solution, part of the dye is secreted into the tracheal lumen. This basal secretion is increased by both parasympathomimetics and sympathomimetics. In addition, expectorants are also capable of increasing tracheal phenol red output. Therefore this method is suitable for the study of drugs that may be capable of influencing tracheobronchial secretion.