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Recently, tablets inscribed with the Mitsubishi 3-diamond logo, and sold as 3,4-methylenedioxymethamphetamine (MDMA), were found to contain p-methoxymethamphetamine (PMMA), a compound with MDMA-like effects. Shortly after this first submission, similarly inscribed tablets were encountered containing both PMMA and p-methoxyamphetamine (PMA). This second tablet composition has been implicated in several recent deaths in the US. Because two other positions are available for mono-methoxy substitution on the phenyl ring, it is essential that the correct identification be made for these compounds. Analytical data are supplied to enable differentiation of these ring isomers as well as the ketones that serve as their precursors.

Objetivo: Determinar a eficácia e tolerabilidade de 4 substâncias calorigênicas: ioimbina, triiodotironina (T3), combinação efedrina-aminofilina e fenilpropanolamina (FPA). Material, Métodos e Desenho da Pesquisa: 103 mulheres obesas (30 < BMI < 40kg/m²), de 18 a 55 anos, foram submetidas a estudo cego comparativo das 4 substâncias associadas a uma dieta com 1.200 calorias (55% HC, 30% gordura e 15% proteínas). As doses utilizadas foram 8mg de ioimbina, 25mcg de T3, 100mg de aminofilina + 25mg de efedrina e 25mg de FPA. Foi ainda incluído um grupo placebo. Os 4 medicamentos e o placebo foram dados 3 vezes ao dia, antes do desjejum, do almoço e do jantar. O estudo se realizou num período de 12 semanas, para cada paciente e no início e o fim do mesmo foram avaliados peso, composição corpórea por bioimpedância, metabolismo de repouso (por calorimetria), pulso e pressão arterial e eventos adversos. Resultados: Houve perda de peso em todos os grupos, mas o único que perdeu peso significativamente em relação ao grupo placebo foi o que recebeu FPA (p < 0,05). Não houve diferença quanto à composição corpórea e metabolismo de repouso entre os 5 grupos. Conclusão: Em nossa amostra, a FPA se revelou mais eficaz, embora este fato não possa ser atribuído a uma maior queima energética em repouso, já que não houve diferença apreciável no metabolismo de repouso entre os grupos. Objective: To determine weight loss efficacy of four thermogenic drugs often used in obesity treatment. Design, Material and Methods: 103 obese women (30 < BMI < 40kg/m²) aged 18 to 55 years-old were assigned to receive in a blind protocol and by random order yohimbine 8mg, triiodothyronine (T3) 25mcg, amminophiline 100mg plus ephedrine 25mcg, phenylpropanolamine (PPA) 25mcg or placebo t.i.d. for 12 weeks. They received a 1,200kcal diet and were evaluated every two weeks for weight, blood pressure, heart rate, adverse events and adherence. Each subject was submitted to bioimpedance and calorimetry analysis in the beginning and in the end of the study. Results: Patients who were taking PPA lost significantly more weight (measured by DBMI) as compared to the other groups in relation to placebo group (p < 0.05). Changes in percentual fat mass, percentual lean body mass and calorimetry analysis showed no significant differences between the groups. Conclusion: PPA can be considered the best drug in respect of short-term weight loss, but we cannot explain this fact on increase in the resting metabolic rate, which was not different among the groups.

A total of eight isomeric phenylpropanolamines are possible when the terminal amine is either an N -monomethylamine or a primary amine: (−)ephedrine, (+)ephedrine, (+)pseudoephedrine, (−)pseudoephedrine, (−)norephedrine, (+)norephedrine, (+)cathine, and (−)cathine. Few previous studies have examined the individual optical isomers of these phenylpropanolamines and, with the exception of one report on locomotor effects, no comparative behavioral data have been published on this series of agents. Using rats trained to discriminate 4 mg/kg of (−)ephedrine (i.p.) from saline vehicle using standard operant conditioning with a VI 15-s schedule of reinforcement, all eight agents were examined in tests of stimulus generalization. The (−)ephedrine stimulus (ED 50 =0.90 mg/kg) generalized to (+)ephedrine (ED 50 =2.64 mg/kg), (+)pseudoephedrine (ED 50 =6.58 mg/kg), (−)norephedrine (ED 50 =1.86 mg/kg), (+)norephedrine (ED 50 =5.75 mg/kg), and (+)cathine (ED 50 =4.87 mg/kg). The (−)ephedrine stimulus failed to generalize to either (−)pseudoephedrine or (−)cathine; the latter agents produced a maximum of 29 and 31% (−)ephedrine-appropriate responding, respectively. Thus, (a) six of the eight phenylpropanolamines produced ephedrine-like stimulus effects, (b) (−)ephedrine was the most potent of the examined agents, and (c) where stimulus generalization occurred, ED 50 values spanned less than a tenfold range.

Scope: The only treatment available for coeliac disease (CD) is a strict diet in which the intake of wheat, barley, rye, or oats is avoided. Barley is a major cereal crop, grown mainly for its use in brewing, and it has high nutritional value. The identification of varieties with a reduced toxicity profile may contribute to improve the diet, the quality of life and health of CD patients. Methods and results: Searching for harmless barleys, we investigated accessions of malting and wild barley, used for developing new cultivated cereals. The CD toxicity profile of barleys was screened using G12 antibody and cell proliferation and IFN-γ release from peripheral blood mononuclear cells and intestinal biopsies from CD patients. We found a direct correlation between the reactivity with G12 and the immunogenicity of the different barleys. Conclusion: The malting barleys were less immunogenic, with reduced levels of toxic gluten, and were possibly less harmful to CD patients. Our findings could raise the prospect of breeding barley species with low levels of harmful gluten, and the attractive goal of developing nontoxic barley cultivars, always taking into account the Codex standard for foods for special dietary use for persons intolerant to gluten. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim., The Spanish Ministry of Science and Innovation (AGL2010-19643-C02-02 and TRA2009_0047), the European Regional Development Fund (FEDER), and the Junta de Andalucía (Project P09AGR-4783) supported this work.

Stereoisomeric identification of norephedrine (NE) derived from methamphetamine (MA) or amphetamine (AM) was investigated by SIM-GC/MS assay using the urine of 33 MA abusers and 1 AM abuser. The assay simultaneously identified TFA-derivatized MA and AM metabolites, including AM, p-hydroxyl-MA (p-HMA), and p-hydroxyl-AM (p-HAM). The analysis lasted approximately 43 min, with a signal-to-noise ratio ofor=3 and a detection limit of 50 ng/mL. Among 12 urine samples from different subjects, only the S (+) form of MA and its metabolites (AM, p-HMA, p-HAM) was detected, however, a (1R,2S)-(-)-NE stereoisomer was also identified. Among the urine samples of two subjects, only the R (-) form of MA and its metabolites (AM, p-HMA, p-HAM) was detected, while NE was not detected. Following urinalysis of urine obtained from 19 MA abusers and 1 AM abuser, only the (1R,2S)-(-)-NE stereoisomer was identified, while unmetabolized MA, AM, and their metabolites (p-HMA, p-HAM), showed stereoselective metabolism. Although (1R,2S)-(-)-ephedrine (EP) alone was found in the urine of 1 (S)-(+)-MA user and 1 (S)-(+)- and (R)-(-)-MA user among 33 MA users, it was not present in the urine of the remaining 31 subjects. Therefore, (1R,2S)-(-)-NE was likely not of (1R,2S)-(-)-EP origin and was most likely from (S)-(+)-AM of the MA metabolite. The production ratio of (1R,2S)-(-)-NE to (S)-(+)-AM ranged from 0.01 to 0.25 in MA abusers and was 0.12 in AM abusers.

A novel enantioselective alkylation of double benzylic substrates with secondary electrophiles is reported. A simple norephedrine-based chiral ligand was synthesized that gives alkylation product in 95% yield and 95% ee. A unique water effect on the enantioselectivity was unveiled. Good to excellent ee values were obtained with a number of double benzylic substrates and secondary electrophiles. This novel reaction has been applied to the synthesis of a promising anticancer agent.

Phenylpropanolamine (PPA) is a sympathetic amine used in over-the-counter cold remedies and weight-control preparations worldwide. Its use has been associated with hypertensive episodes and hemorrhagic strokes in younger women. Several reports have linked the abuse of PPA with myocardial injury, especially when overdose is involved. We report here the first case of Dexatrim (PPA)-induced myocardial injury in a young woman who was using it at recommended doses for weight control. In addition, we review the 7 other cases of PPA related myocardial injury that have been reported so far. Physicians and patients should be alert to the potential cardiac risk associated with the use of PPA, even at doses generally considered to be safe. (Heart Lung® 2003;32:100-4.)

In this study, we sought to elucidate whether phenylpropanolamine (PPA) in cold remedies (small and divided doses) increases the risk of hemorrhagic stroke (HS). PPA exposure significantly increased the risk, and the risk was much higher in women. In women, linear trends were also found in recency, duration, and dosage of PPA exposure. PPA contained in cold remedies increases the risk of HS, particularly in women.

Background: Overactive bladder (OAB) is associated with high healthcare costs, which may be partially driven by drug treatment. There is little comparative data on antimuscarinic drugs with respect to resource use and costs. This study was conducted to address this gap and the growing need for naturalistic studies comparing health economics outcomes in adult patients with OAB syndrome initiating treatment with different antimuscarinic drugs in a primary care setting in Spain. Methods: Medical records from the databases of primary healthcare centres in three locations in Spain were assessed retrospectively. Men and women >= 18 years of age who initiated treatment with fesoterodine, tolterodine or solifenacin for OAB between 2008 and 2010 were followed for 52 weeks. Healthcare resource utilization and related costs in the Spanish National Health System were compared. Comparisons among drugs were made using multivariate general linear models adjusted for location, age, sex, time since diagnosis, Charlson comorbidity index, and medication possession ratio. Results: A total of 1,971 medical records of patients (58.3% women; mean age, 70.1 [SD: 10.6] years) initiating treatment with fesoterodine (n = 302), solifenacin (n = 952) or tolterodine (n = 717) were examined. Annual mean cost per patient was (sic)1798 (95% CI: (sic)1745; (sic)1848). Adjusted mean (95% bootstrap CI) healthcare costs were significantly lower in patients receiving fesoterodine ((sic)1639 [1542; 1725]) compared with solifenacin ((sic)1780 [(sic)1699; (sic)1854], P = 0.022) or tolterodine ((sic)1893 [(sic)1815; (sic)1969], P = 0.001). Cost differences occurred because of significantly fewer medical visits, and less use of absorbent products and OAB-related concomitant medication in the fesoterodine group. Conclusions: Compared with solifenacin and tolterodine, fesoterodine was a cost-saving therapy for treatment of OAB in the primary care setting in Spain., This study was sponsored by Pfizer Inc. Javier Rejas and Marion Kvasz are employees of Pfizer, S.L.U. and Pfizer PIO, respectively. Antoni Sicras was a paid consultant to Pfizer in connection with the development of this manuscript. Statistical analysis was performed by DataClinics and was funded by Pfizer Inc. All other authors declare that they have no competing interests. Editorial support was provided by Colin Mitchell, PhD, of Complete Healthcare Communications, Inc., and was funded by Pfizer Inc.