Amphétamine | EPFL Graph Search

L’amphétamine (DCI) est une substance sympathicomimétique aux effets anorexigènes et psychoanaleptiques. L'amphétamine est utilisée chez les enfants et adultes dans le traitement du TDAH, de la narcolepsie, de l'obésité, et des troubles de l'hyperphagie boulemique, mais son usage non médical est criminalisé dans la plupart des pays du monde. Ses usages non médicaux incluent l'amélioration de la performance sportive, et l'usage récréatif comme euphorisant et aphrodisiaque. L'amphétamine était utilisée en guerre pour améliorer la performance, principalement dans le cadre de privation de sommeil. Étymologie Le nom amphétamine trouve son origine de ses noms chimiques et est une abréviation dont voici l'étymologie : l'amphétamine, c'est une phénéthylamine à laquelle a été ajouté un groupement méthyle (-CH3) en position α (alpha) de sa chaîne, ce qui donne alpha-méthyl-phénéthylamine ; c'est la version développée. Du nom alpha-méthyl-phénéthylamine ne seront retenues par si

Dopamine Transporter, PhosphoSerine129 alpha-Synuclein and alpha-Synuclein Levels in Aged LRRK2 G2019S Knock-In and Knock-Out Mice

Salvatore Novello

The G2019S mutation in leucine rich-repeat kinase 2 (LRRK2) is a major cause of familial Parkinson's disease. We previously reported that G2019S knock-in mice manifest dopamine transporter dysfunction and phosphoSerine129 alpha-synuclein (pSer129 alpha-syn) immunoreactivity elevation at 12 months of age, which might represent pathological events leading to neuronal degeneration. Here, the time-dependence of these changes was monitored in the striatum of 6, 9, 12, 18 and 23-month-old G2019S KI mice and wild-type controls using DA uptake assay, Western analysis and immunohistochemistry. Western analysis showed elevation of membrane dopamine transporter (DAT) levels at 9 and 12 months of age, along with a reduction of vesicular monoamine transporter 2 (VMAT2) levels at 12 months. DAT uptake was abnormally elevated from 9 to up to 18 months. DAT and VMAT2 level changes were specific to the G2019S mutation since they were not observed in LRRK2 kinase-dead or knock-out mice. Nonetheless, dysfunctional DAT uptake was not normalized by acute pharmacological inhibition of LRRK2 kinase activity with MLi-2. Immunoblot analysis showed elevation of pSer129 alpha-syn levels in the striatum of 12-month-old G2019S KI mice, which, however, was not confirmed by immunohistochemical analysis. Instead, total alpha-syn immunoreactivity was found elevated in the striatum of 23-month-old LRRK2 knock-out mice. These data indicate mild changes in DA transporters and alpha-syn metabolism in the striatum of 12-month-old G2019S KI mice whose pathological relevance remains to be established.

MDPI2022

Isocyanoacetates as Synthetic Platform Towards Natural Products and Biologically Relevant Scaffolds

Thomas Bertrand Pascal Marie Buyck

My PhD work started with the development of a racemic access to trigonoliimine B, an hexacyclic alkaloid isolated in 2010. After having explored different strategies, we reported a 7-step synthesis of this natural product. This synthesis features a challenging and unprecedented Bischler-Napieralski reaction for the formation of a 7-membered ring with the concurrent creation of an exocyclic imine at the last step. The choice of sulfolane as solvent for this transformation was critical to the success. Aiming at upgrading our synthesis towards an enantioselective version, we developed an enantioselective synthesis of α-quaternary α-amino acids. The Michael addition between α-aryl isocyanoacetates and phenyl vinyl selenone catalyzed by a quinine derivative affords enantioenriched Michael adducts. Due to the nature of the functional groups, these adducts are easily transformed to useful scaffolds such as pyrrolidinones and oxindoles. We also demonstrated the synthetic utility of this transformation by using it for the enantioselective total synthesis of (+)- and (-)-trigonoliimine A. With the idea to further demonstrate the efficiency of this reaction for natural product synthesis, we are trying to develop the first total synthesis of (+)-hinckdentine A. Finally, during our investigations on the Michael adduct, we observed the formation of 1,3-oxazinan-2-one. We implemented an integrated one-pot process to access biologically relevant 1,3-oxazinan-2-one. We also studied the reaction mechanism demonstrating an unprecedented triple role of phenyl selenonyl group as an electron withdrawing group, a leaving group and a latent oxidant.

EPFL2014

Free operant and discrete trial performance of mice in the nine-hole box apparatus: validation using amphetamine and scopolamine

Jean-Charles Bensadoun

RATIONALE: To determine the suitability of the nine-hole box to characterise mouse performance on a free operant task and a discrete trials task, and to validate the tests by probing whether d-amphetamine and scopolamine modify performance of the task as predicted. OBJECTIVES: To demonstrate the functionality and efficiency of the mouse nine-hole box for the evaluation of performance under fixed- (FR) and progressive-ratio (PR) operant schedules, as well as under a three-choice visual discrimination task and subsequent reversals of the task. In addition, sensitivity of the apparatus was assessed using pharmacological challenges. METHODS: C57BL/6J were tested on CRF, FR5, FR10, FR20, and a modified PR3 schedule. Behavioural response to d- amphetamine sulphate (0.1, 0.3, and 2.0 mg/kg for FR and 0.1, 0.3, and 1.0 mg/kg for PR) was assessed. In a separate group of mice trained on a three- choice visual discrimination task, the task was reversed (light+, dark+, light+, dark+) 3 times to determine acquisition and reversal of the visual discrimination rule. Scopolamine hydrobromide was examined in this paradigm with the reversal task, and was used to determine learning acquisition and rule reversal learning. RESULTS: Mice rapidly acquired the FR and PR schedules, as well as both three-choice visual discrimination procedures in the nine-hole box. d-Amphetamine significantly reduced performance on the FR5 and FR10 schedules as shown by the reduction in the number of rewarded responses and the increases in various latency measurements. As expected, d-amphetamine induced an increase in the break point and eliminated the pauses that occurred on high ratio schedules under the PR3 paradigm. Pretreatment of scopolamine decreased accuracy in the three-choice visual discrimination task. CONCLUSIONS: The nine-hole box is an effective tool to assess operant behaviours in mice following pharmacological manipulation validating the utility of this apparatus for the behavioural evaluation of drug-induced and transgenic models of neurodegenerative disorders.

2004

Free operant and discrete trial performance of mice in the nine-hole box apparatus: validation using amphetamine and scopolamine

Jean-Charles Bensadoun

2004