A5087482611- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Mast cells and histamine
- Epilepsy research and treatment
- Neuropeptides and Animal Physiology
- Asthma and respiratory diseases
- Ion channel regulation and function
- Allergic Rhinitis and Sensitization
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Pharmacological Effects and Toxicity Studies
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Phosphodiesterase function and regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Pharmacological Effects and Assays
- SARS-CoV-2 detection and testing
- Dermatology and Skin Diseases
- Cholinesterase and Neurodegenerative Diseases
- Adenosine and Purinergic Signaling
- Neurological disorders and treatments
- Zebrafish Biomedical Research Applications
- Urticaria and Related Conditions
UCB Pharma (Belgium)
2015-2025
Alliance Université-Entreprise de Grenoble
2022
University of Bonn
2017
Université Toulouse III - Paul Sabatier
2006
Inserm
2006
Naresuan University
2004
Vrije Universiteit Amsterdam
2004
Institute of Pathology and Genetics
2002
Université Libre de Bruxelles
1989
Medical University of South Carolina
1989
(S)-alpha-ethyl-2-oxopyrrolidine acetamide 2 (levetiracetam, Keppra, UCB S.A.), a structural analogue of piracetam, has recently been approved as an add-on treatment refractory partial onset seizures in adults. This drug appears to combine significant efficacy and high tolerability due unique mechanism action. The latter relates brain-specific binding site for (LBS levetiracetam site) that probably plays major role its antiepileptic properties. Using this novel molecular target, we initiated...
Competition experiments with [(3)H]mepyramine showed that cetirizine and its enantiomers, levocetirizine (S)-cetirizine, bound high affinity stereoselectivity to human H(1) histamine receptors (K(i) values of 6, 3, 100 nM, respectively). Cetirizine were 600-fold more selective for compared a panel channels. Binding results indicated the interaction between cetirizine, is compatible competitive behavior, in contrast noncompetitive profile observed isolated organs. kinetics provided suitable...
Replacement of the lost myelin sheath is a therapeutic goal for treating demyelinating diseases central nervous system (CNS), such as multiple sclerosis (MS). The G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR17, which phylogenetically closely related to receptors "purinergic cluster," has emerged modulator CNS myelination. However, whether GPR17-mediated signaling positively or negatively regulates this critical process unresolved. We identified...
Lilly/Avid's AV-1451 is one of the most advanced tau PET tracers in clinic. Although results obtained Alzheimer's disease patients are compelling, discrimination tracer uptake healthy individuals and with supranuclear palsy (PSP) less clear as there substantial overlap signal multiple brain regions. Moreover, accurate quantification [18 F]AV-1451 may not be possible.The aim present study was to characterize vitro binding understand identify potential off-target that could explain poor...
Synaptic vesicle protein 2A (SV2A) constitutes a distinct binding site for an antiepileptic drug levetiracetam (Keppra). In the present study we characterized SV2A (+/-) heterozygous mice in several seizure models and tested if anticonvulsant efficacy of is reduced these mice.Seizure thresholds male their wild-type littermates were assessed pilocarpine (i.p.), kainic acid (s.c.), pentylenetetrazol (i.v.), 6-Hz maximal electroshock models. Kindling development was compared amygdala corneal...
Rotigotine acts as a dopamine receptor agonist with high affinity for the D2, D3, D4 and D5 receptors but low D1 receptor. We have investigated this further in radioligand binding functional studies compared profile of rotigotine that other drugs used treatment Parkinson's disease (PD).
Brivaracetam (BRV) and levetiracetam (LEV) are effective antiepileptic drugs that bind selectively to the synaptic vesicle 2A (SV2A) protein. However, BRV differs from LEV in it exhibits more potent complete seizure suppression animal models including amygdala-kindled mice, where afforded nearly suppression. This raises possibility aside potency differences, may interact differently with SV2A protein, which is not apparent radioligand-binding competition studies. In this study, we used a...
Synaptic vesicle protein 2 isoforms are critical for proper nervous system function and involved in trafficking. The synaptic 2A (SV2A) isoform has been identified as the binding site of antiepileptic levetiracetam (LEV), making it an interesting therapeutic target epilepsy. (18)F-UCB-H is a novel PET imaging agent with nanomolar affinity human SV2A.Preclinical studies were performed isoflurane-anesthetized rats. arterial input was measured arteriovenous shunt β-microprobe system. injected...
Recent studies have recognized G protein-coupled receptors as important regulators of oligodendrocyte development. GPR17, in particular, is an orphan receptor that has been identified oligodendroglial maturation inhibitor because its stimulation arrests primary mouse oligodendrocytes at a less differentiated stage. However, the intracellular signaling effectors transducing activation remain poorly understood. Here, we use Oli-neu cells, immortalized cell line derived from murine...
We compared the binding of [N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) and pirenzepine to muscarinic receptors in four regions rat central nervous system (cortex, hippocampus, striatum, cerebellum) heart. Equilibrium studies suggested existence three classes receptors: A, with high affinity for [3H] NMS (in cortex, striatum); B, intermediate [3H]NMS same brain regions); C, low cerebellum heart). Dissociation kinetic indicated that receptor types C had different koff values allowing,...
Padsevonil is an antiepileptic drug (AED) candidate synthesized in a medicinal chemistry program initiated to rationally design compounds with high affinity for synaptic vesicle 2 (SV2) proteins and low-to-moderate the benzodiazepine binding site on GABA<sub>A</sub> receptors. The pharmacological profile of padsevonil was characterized electrophysiological experiments. At recombinant SV2 proteins, padsevonil's SV2A greater than that levetiracetam brivaracetam (pKi 8.5, 5.2, 6.6,...
SUMMARY Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in the mTOR pathway genes TSC1 or TSC2 . TSC can affect multiple organs including brain, and most patients (75-90%) present with seizures during early childhood intractable epilepsy throughout life. inhibitors, part of current standard care, lack optimal characteristics to fully address patient phenotypes. Here, we report on application our all-optical electrophysiology platform for phenotypic screening...
We previously observed that [3H]NMS recognizes three types of muscarinic receptors in rat brain (one M1 subclass with high affinity for pirenzepine, and two M2 subclasses low affinities pirenzepine), based on distinct kinetic constants these subclasses. In this work, we investigated the binding four selective antagonists to (the M2) were able demonstrate cardiac-like pirenzepine N-methylscopolamine present not only cerebellum (as shown; see introduction) but also cortex, striatum,...