Dopamine receptors in GtoPdb v.2023.1

Dopamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Dopamine Receptors [373]) are commonly divided into D1-like (D1 and D5) and D2-like (D2, D3 and D4) families, where the endogenous agonist is dopamine

Dopamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Dopamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Dopamine Receptors [363]) are commonly divided into D1-like (D1 and D5) and D2-like (D2, D3 and D4) families, where the endogenous agonist is dopamine

Le processus de découverte du médicament dans l'industrie pharmaceutique

Cet article fait le point sur le processus suivi dans l'Industrie Pharmaceutique pour découvrir de nouveaux médicaments innovants issus de la chimie médicinale ou des médicaments biologiques. Après quelques généralités décrivant le processus global de Recherche et de Développement (contenu des études précliniques et cliniques), les différentes étapes impliquées spécifiquement dans la phase de Recherche Amont (période allant de la conception initiale d'un programme de recherche jusqu'à la proposition d'un candidat au développement) sont analysées en détail. En ce qui concerne les composés issus de la chimie médicinale, sont successivement abordés: le choix de la cible biologique (moléculaire ou cellulaire) et sa validation fonctionnelle, les techniques de criblage des librairies chimiques, la recherche de composés constituant des têtes de série chimiques optimisables, l'optimisation finale des têtes de série en candidats médicaments qui seront proposés au développement préclinique et clinique. En ce qui concerne les biomédicaments, le processus utilisé pour la génération et la production des anticorps monoclonaux humanisés (nus ou conjugués) et des protéines thérapeutiques recombinantes est discuté en détail

Evaluation du potentiel thérapeutique de l'aspirine R et du SL25.1131 (un IMAO mixte réversible) dans un modèle de la maladie de parkinson chez la souris (MPTP)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Physiopathologie et génétique de l’épilepsie : données récentes

Des stratégies nouvelles sont nécessaires pour le traitement de l’épilepsie, du point de vue de l’efficacité, de la sécurité et de la prévention. La recherche d’anti-épileptiques innovants est basée sur le choix de cibles biologiques appropriées, parmi lesquelles les plus pertinentes semblent être les canaux chlore et potassium. L’analyse transcriptomique/protéomique est également susceptible de révéler des gènes ou des protéines impliquées dans la maladie, notamment par la comparaison entre biopsies de tissu cérébral sain et épileptique. Des modèles génétiques animaux permettent d’analyser des épilepsies dont l’étiologie est unique. Enfin certaines cibles peuvent être découvertes fortuitement à l’occasion de programmes de recherche portant sur d’autres domaines, notamment sur les cytokines pro-inflammatoires

The quantification of brain lesions with an omega 3 site ligand: a critical analysis of animal models of cerebral ischaemia and neurodegeneration.

International audiencePrevious investigations have indicated that the detection and quantification of omega 3 (peripheral type benzodiazepine) binding site densities that are associated with reactive astroglia and macrophages could be of widespread applicability in the localization and indirect assessment of neural tissue damage in the central nervous system. In the present study, we analyze the usefulness of this approach in a number of experimental models that are characterized by (or putatively involve) neuronal degeneration. One week after the systemic administration of the excitotoxin, kainate, a marked increase in omega 3 site densities (as assessed by [3H]PK 11195 binding) was noted, an increase that was most prominent in known regions of selective vulnerability (hippocampus and septum). However, the kainate-induced omega 3 site proliferation was not a function of the dose administered, a marked interstudy variation was observed, and the binding increase was prevented by the administration of the anticonvulsant, clonazepam. The densities of omega 3 sites were studied, by autoradiography (using [3H]PK 11195 or [3H]PK 14105 as ligands), in 4 groups of Fischer 344 rats aged 3, 12, 22 and 30 months. No age-related changes were noted except in the 30-month-old group in which discrete and focal increases (reflecting tumoral processes) were observed in various brain regions. In spontaneously hypertensive, stroke-prone rats, omega 3 binding increases were observed concomitant with the development of stroke-related neurological signs. With autoradiography, the omega 3 site increase was localized to focal increases in the boundary zones between major cerebral arteries (and corresponding to regions of ischaemic or haemorrhagic infarction). Focal cerebral ischaemia was studied in rats and mice. Subsequent to middle cerebral artery occlusion in normotensive (Wistar/Kyoto) and spontaneously hypertensive rats, the density of omega 3 sites in the ipsilateral hemisphere was markedly elevated, the increase being greater in the spontaneously hypertensive rats. The increases in omega 3 labelling in these two strains matched the absolute volumes of infarctions, determined previously. Middle cerebral artery occlusion in the mouse also increased hemispheric levels of omega 3 sites; the maximum values were obtained between 4 and 8 days following the induction of focal ischaemia. These results demonstrate the feasibility of using omega 3 sites as a marker of excitotoxic, ischaemic and proliferative damage in the rodent brain. Binding measurement in tissue homogenates is an economic and time-efficient approach, whereas the autoradiographic detection of omega 3 sites allows the localization of brain lesions with a macroscopic or microscopic level of anatomical resolution.(ABSTRACT TRUNCATED AT 400 WORDS

Consequences of Extended Spectrum Beta‐Lactamase–Producing Enterobacteriaceae and Methicillin‐Resistant Staphylococcus aureus Carriage in Awaiting Liver Transplant Patients

International audienceInfections in patients with cirrhosis are associated with liver‐related complications (LRCs), especially in patients awaiting liver transplantation (LT). The aim of this study was to evaluate the impact of methicillin‐resistant Staphylococcus aureus (MRSA) and extended spectrum beta‐lactamase colonization on infections and LRCs for patients on the wait list and on infections after LT. We retrospectively included 250 of 483 patients with cirrhosis who were placed on the wait list for LT from December 2015 to January 2018. These patients were screened for MRSA or extended spectrum beta‐lactamase–producing Enterobacteriaceae (ESBLE) at the time of wait‐list placement and after LT. Of the patients, 76% were male with a mean age of 57.5 ± 10 years, and the most frequent cause of liver disease was alcohol (39%). Median Model for End‐Stage Liver Disease (MELD) score was 19 (12‐28). Only 1 patient was positive for MRSA; 19% of patients (n = 47) had ESBLE fecal carriage at the time of wait‐list placement and 15% (n = 37) had it after LT. Infection‐free survival on the wait list and after LT, according to fecal carriage status, was not statistically different between 2 groups. LRC‐free survival at 6 and 12 months was significantly lower in ESBLE fecal carriage (HR, 1.6; P = 0.04). MELD score >19 (HR, 3.0; P = 0.01) and occurrence of infection during the first 3 months on the wait list (HR, 4.13; P < 0.001) were independent risk factors for LRC occurrence in the multivariate analysis. Our study is the first showing that in a cohort of patients with cirrhosis waiting for LT LRC‐free survival was lower in patients with ESBLE fecal carriage but that infection‐free survival was not different between the 2 groups

Consequences of Extended Spectrum Beta-Lactamase\u2013Producing Enterobacteriaceae and Methicillin-Resistant Staphylococcus aureus Carriage in Awaiting Liver Transplant Patients

Infections in patients with cirrhosis are associated with liver-related complications (LRCs), especially in patients awaiting liver transplantation (LT). The aim of this study was to evaluate the impact of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase colonization on infections and LRCs for patients on the wait list and on infections after LT. We retrospectively included 250 of 483 patients with cirrhosis who were placed on the wait list for LT from December 2015 to January 2018. These patients were screened for MRSA or extended spectrum beta-lactamase\u2013producing Enterobacteriaceae (ESBLE) at the time of wait-list placement and after LT. Of the patients, 76% were male with a mean age of 57.5&nbsp;\ub1&nbsp;10 years, and the most frequent cause of liver disease was alcohol (39%). Median Model for End-Stage Liver Disease (MELD) score was 19 (12-28). Only 1 patient was positive for MRSA; 19% of patients (n&nbsp;=&nbsp;47) had ESBLE fecal carriage at the time of wait-list placement and 15% (n&nbsp;=&nbsp;37) had it after LT. Infection-free survival on the wait list and after LT, according to fecal carriage status, was not statistically different between 2 groups. LRC-free survival at 6 and 12&nbsp;months was significantly lower in ESBLE fecal carriage (HR, 1.6; P =&nbsp;0.04). MELD score &gt;19 (HR, 3.0; P&nbsp;=&nbsp;0.01) and occurrence of infection during the first 3&nbsp;months on the wait list (HR, 4.13; P&nbsp;&lt;&nbsp;0.001) were independent risk factors for LRC occurrence in the multivariate analysis. Our study is the first showing that in a cohort of patients with cirrhosis waiting for LT LRC-free survival was lower in patients with ESBLE fecal carriage but that infection-free survival was not different between the 2 groups