Promotions prédatrice et coopérative sur le marché des médicaments

Ce papier propose un modèle de différenciation horizontale afin d'analyser la concurrence en promotion sur le marché pharmaceutique. La promotion pharmaceutique cible à la fois le médecin et le patient. Néanmoins, la nature de ces stratégies diffère : la promotion orientée vers le consommateur (POC) élève la demande de marché et la promotion orientée vers le médecin (POM) augmente la part de marché. Dans un cadre théorique, nous obtenons un résultat principal. D'une part, la profitabilité de la POM s'élève avec les dépenses de POC du concurrent, et celle de la POC baisse avec les dépenses de POM de son concurrent

Tarif forfaitaire de responsabilité : quels impacts sur le pharmacien ?

L'objectif de cet article est d'étudier l'impact du tarif forfaitaire de responsabilité (TFR) sur la part de la marge du grossiste attribuée au pharmacien et sur l'effort de substitution entre marque et générique. Nous considérons une situation dans laquelle le génériqueur vend directement son générique au pharmacien et le laboratoire de marque vend son princeps par l'intermédiaire d'un grossiste. Nous supposons que les produits sont verticalement différenciés et nous résolvons un jeu en deux étapes. A la première étape, le génériqueur détermine la part de la marge du grossiste qu'il consent au pharmacien afin de l'inciter à substituer et, si un tarif forfaitaire de responsabilité est introduit, les firmes se concurrencent en prix. A la seconde étape, le pharmacien choisit son effort de substitution. Nous montrons que l'introduction du TFR augmente la part de la marge du grossiste allouée au pharmacien par le génériqueur, mais diminue l'effort de substitution du pharmacien

Pseudo-génériques et fusions « stratégiques » dans l’industrie du médicament

Cet article comble le manque de littérature théorique concernant les fusions entre laboratoires de marque et laboratoires de génériques sur les marchés pharmaceutiques. Afin d’empêcher les firmes de génériques d’accroître leurs parts de marché, certaines firmes de marque produisent elles-mêmes des génériques, appelés pseudo-génériques. Nous montrons, pour un duopole à biens substituables dans lequel une firme de marque concurrence à la Cournot une firme de générique, que la firme de marque est toujours incitée à racheter son concurrent et très souvent à produire des pseudo-génériques.This paper fills the gap in the theoretical literature concerning mergers between brand-name and generic laboratories in pharmaceutical markets. To prevent generic firms from increasing their market share, some brand-name firms produce generics themselves, called pseudo-generics. We show, in a duo-poly model with substitutable goods, in which a brand-name firm and a generic firm compete à la Cournot, that a brand-name company always has an incentive to purchase its competitor, and often, an incentive to produce pseudo-generics

PHENOPSIS DB: an Information System for Arabidopsis thaliana phenotypic data in an environmental context

<p>Abstract</p> <p>Background</p> <p>Renewed interest in plant × environment interactions has risen in the post-genomic era. In this context, high-throughput phenotyping platforms have been developed to create reproducible environmental scenarios in which the phenotypic responses of multiple genotypes can be analysed in a reproducible way. These platforms benefit hugely from the development of suitable databases for storage, sharing and analysis of the large amount of data collected. In the model plant <it>Arabidopsis thaliana</it>, most databases available to the scientific community contain data related to genetic and molecular biology and are characterised by an inadequacy in the description of plant developmental stages and experimental metadata such as environmental conditions. Our goal was to develop a comprehensive information system for sharing of the data collected in PHENOPSIS, an automated platform for <it>Arabidopsis thaliana </it>phenotyping, with the scientific community.</p> <p>Description</p> <p>PHENOPSIS DB is a publicly available (URL: <url>http://bioweb.supagro.inra.fr/phenopsis/</url>) information system developed for storage, browsing and sharing of online data generated by the PHENOPSIS platform and offline data collected by experimenters and experimental metadata. It provides modules coupled to a Web interface for (i) the visualisation of environmental data of an experiment, (ii) the visualisation and statistical analysis of phenotypic data, and (iii) the analysis of <it>Arabidopsis thaliana </it>plant images.</p> <p>Conclusions</p> <p>Firstly, data stored in the PHENOPSIS DB are of interest to the <it>Arabidopsis thaliana </it>community, particularly in allowing phenotypic meta-analyses directly linked to environmental conditions on which publications are still scarce. Secondly, data or image analysis modules can be downloaded from the Web interface for direct usage or as the basis for modifications according to new requirements. Finally, the structure of PHENOPSIS DB provides a useful template for the development of other similar databases related to genotype × environment interactions.</p

Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization

μ‐Opioid receptors (μ‐ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ‐ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ‐OR antagonist E‐p‐nitrocinnamoylamino‐dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single‐molecule imaging of μ‐ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ‐ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ‐ORs interact with each other to form short‐lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ‐OR pharmacology at single‐molecule level

Signaling from β1- and β2-adrenergic receptors is defined by differential interactions with PDE4

β1- and β2-adrenergic receptors (βARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by β1AR but not β2AR signaling, and chronic stimulation of the two receptors has opposing effects on myocyte apoptosis and cell survival. Differences in the assembly of macromolecular signaling complexes may explain the distinct biological outcomes. Here, we demonstrate that β1AR forms a signaling complex with a cAMP-specific phosphodiesterase (PDE) in a manner inherently different from a β2AR/β-arrestin/PDE complex reported previously. The β1AR binds a PDE variant, PDE4D8, in a direct manner, and occupancy of the receptor by an agonist causes dissociation of this complex. Conversely, agonist binding to the β2AR is a prerequisite for the recruitment of a complex consisting of β-arrestin and the PDE4D variant, PDE4D5, to the receptor. We propose that the distinct modes of interaction with PDEs result in divergent cAMP signals in the vicinity of the two receptors, thus, providing an additional layer of complexity to enforce the specificity of β1- and β2-adrenoceptor signaling

The molecular basis of polysaccharide cleavage by lytic polysaccharide monooxygenases.

Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes that oxidatively break down recalcitrant polysaccharides such as cellulose and chitin. Since their discovery, LPMOs have become integral factors in the industrial utilization of biomass, especially in the sustainable generation of cellulosic bioethanol. We report here a structural determination of an LPMO-oligosaccharide complex, yielding detailed insights into the mechanism of action of these enzymes. Using a combination of structure and electron paramagnetic resonance spectroscopy, we reveal the means by which LPMOs interact with saccharide substrates. We further uncover electronic and structural features of the enzyme active site, showing how LPMOs orchestrate the reaction of oxygen with polysaccharide chains.We thank K. Rasmussen and R.M. Borup for experimental assistance, and MAXLAB, Sweden and the European Synchrotron Radiation Facility (ESRF), France, for synchrotron beam time and assistance. This work was supported by the UK Biotechnology and Biological Sciences Research Council (grant numbers BB/L000423 to P.D., G.J.D. and P.H.W., and BB/L021633/1 to G.J.D. and P.H.W.), Agence Française de l'Environnement et de la Maîtrise de l'Energie (grant number 1201C102 to B.H.), the Danish Council for Strategic Research (grant numbers 12-134923 to L.L.L. and 12-134922 to K.S.J.). Travel to synchrotrons was supported by the Danish Ministry of Higher Education and Science through the Instrument Center DANSCATT and the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (grant agreement 283570). L.M., S.F., S.C. and H.D. were supported by Institut de Chimie Moléculaire de Grenoble FR 2607, LabEx ARCANE (ANR-11-LABX-0003-01), the PolyNat Carnot Institute and the French Agence Nationale de la Recherche (PNRB2005-11).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nchembio.202