Pharmakologie und Toxikologie neuer Rauschmittel

In den letzten Jahren haben neue Rauschmittel den Markt überschwemmt. Studien zur Sicherheit gibt es zumeist nicht. Vergiftungen und Todesfälle sind bereits aufgetreten. In dieser Übersicht werden die wesentlichen molekularen Wirkmechanismen und Daten zur klinischen Pharmakologie und Toxikologie der Amphetamin-Derivate, Piperazin-Derivate und neuer synthetischer Cannabinoide vorgestellt. = New designer drugs are flooding the market. Data on safety is almost completely missing. Intoxications and even fatalities have already been reported. In this review, the main molecular mechanisms of action as well as data on clinical pharmacology and toxicology of amphetamine derivatives, piperazines and synthetic cannabinoids are presented

Chiral drug analysis using mass spectrometric detection relevant to research and practice in clinical and forensic toxicology

This paper reviews analytical approaches published in 2002-2012 for chiral drug analysis and their relevance in research and practice in the field of clinical and forensic toxicology. Separation systems such as gas chromatography, high performance liquid chromatography, capillary electromigration, and supercritical fluid chromatography, all coupled to mass spectrometry, are discussed. Typical applications are reviewed for relevant chiral analytes such as amphetamines and amphetamine-derived designer drugs, methadone, tramadol, psychotropic and other CNS acting drugs, anticoagulants, cardiovascular drugs, and some other drugs. Usefulness of chiral drug analysis in the interpretation of analytical results in clinical and forensic toxicology is discussed as well

Investigations on the stereoselectivity of the phase II metabolism of the 3,4-methylenedioxyethylamphetamine (MDEA) metabolites 3,4-dihydroxyethylamphetamine (DHEA) and 4-hydroxy-3-methoxyethylamphetamine (HMEA)

Different elimination was reported for the two enantiomers of the designer drug 3,4-methylenedioxyethylamphetamine (MDEA) in vivo. In the present work, the enantioselectivity of glucuronidation and sulfation of the MDEA phase I metabolites 3,4-dihydroxyethylamphetamine (DHEA) and 4-hydroxy-3-methoxyethylamphetamine (HMEA) was investigated. First, glucuronide standards were synthesized using rat liver microsomes. Incubations were performed with recombinant human UDP-glucuronyltransferases (UGT) and pooled human liver microsomes (pHLM) for glucuronidation and using recombinant human sulfotransferases (SULT) and pooled human liver cytosol (pHLC) for sulfation. Product formation experiments were performed by quantification of the phase II metabolites using liquid chromatography-high-resolution mass spectrometry. Additionally, substrate depletion experiments were conducted by gas chromatography-mass spectrometry after chiral derivatization for sulfation. UGT2B7, 2B15, and 2B17 were involved in glucuronidation of HMEA and SULT1A1 and SULT1A3 and SULT1A3 and SULT1E1 in the sulfation of DHEA and HMEA, respectively. SULTs provided much higher affinity, whereas UGTs showed higher capacities. Marked stereoselectivity could be observed for UGT2B15, UGT2B17, and pHLM toward S-HMEA, for SULT1A3 and pHLC toward S-DHEA and for SULT1A3 and pHLC toward R-HMEA. In conclusion, the phase II metabolism might also contribute to the observed different pharmacokinetic properties of MDEA

Symptoms, toxicities, and analytical results for a patient after smoking herbs containing the novel synthetic cannabinoid MAM-2201

We report a case of intoxication by the synthetic cannabinoid MAM-2201 ([1-(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl)-methanone). A 31-year-old man smoked about 300 mg of a herbal blend. He experienced an acute transient psychotic state with agitation, aggression, anxiety, and vomiting associated with a sympathomimetic syndrome. MAM-2201 was detected and quantified in a plasma sample using liquid chromatography-tandem mass spectrometry (LC–MS–MS). The level was 49 ng/ml 1 h after smoking. The use of other drugs was analytically excluded. The presence of MAM-2201 was confirmed in the herbal blend using gas chromatography–mass spectrometry (GC–MS) and LC–high resolution MS. This is the first description of an analytically confirmed intoxication and of the determination of MAM-2201 in human blood plasma

How Managers Can Deal with Complex Issues: A Semi-Quantitative Analysis Method of Causal Loop Diagrams Based on Matrices

The increasing complexity of the modern world creates both higher risks and new interdependencies in the socioeconomic environment. To cope with these challenges powerful new tools must be applied to find sustainable solutions. System dynamics is a field that offers potential assistance in dealing with complex issues. However, managers and politicians often lack the knowledge and necessary skills to apply quantitative methods in their decision-making process. In contrast, qualitative approaches are easily understood and handled but have limited capacities for analysis. To address this gap, we have developed a bundle of tools tailored for managers and politicians facing complex problems. These tools enable executives to recognize effective levers and assess potential consequences of specific interventions in a highly interconnected system. The approach detailed here equips decision makers with a powerful method to develop, test, and communicate strategies to find long-term sustainable solutions for complex issues in business and society

Cryptic species in the cosmopolitan Bugula neritina complex (Bryozoa, Cheilostomata)

Previous analyses of the mitochondrial gene cytochrome c oxidase subunit 1 (COI) and γ-proteobacterial endosymbiont diversity have suggested that the marine bryozoan Bugula neritina is a complex of three cryptic species, namely Types S, D and N. Types D and N were previously reported to have restricted distributions along California (western USA) and Delaware and Connecticut (eastern USA), respectively, whereas Type S is considered widespread in tropical, subtropical and temperate regions due to anthropogenic transport. Here, Bayesian species delimitation analysis of a data set composed of two mitochondrial (COI and large ribosomal RNA subunit [16S]) and two nuclear genes (dynein light chain roadblock type-2 protein [DYN] and voltage-dependent anion-selective channel protein [VDAC]) demonstrated that Types S, D and N correspond to three biological species. This finding was significantly supported, in spite of the combinations of priors applied for ancestral population size and root age. Furthermore, COI sequences were used to assess the introduction patterns of the cosmopolitan Type S species. Two COI haplotypes of Type S (S1a and S1d) were found occurring at a global scale. Mantel tests showed correlation between these haplotypes and local sea surface temperature tolerance. Accordingly, the distributions of Type S haplotypes may reflect intraspecific temperature tolerance variation, in addition to the role of introduction vectors. Finally, we show that the Type N may also have been introduced widely, as this species was found for the first time in Central California and north-eastern Australia.Center for Marine Biodiversity Research (NP-BioMar, USP)Center for Marine Biology of the University of São Paulo (CEBIMar-USP)#2009/08940-7, São Paulo Research Foundation (FAPESP)#2011/19857-3, FAPESP#2009/08941-3, FAPESPCNPq 151221/2013-8CNPq 564945/2010-2CNPq 142128/2008-2Randolph-MaconCollegeNERC Grant NE/E015298/