title: Rose Bengal analogs and vesicular glutamate transporters (VGLUTs).
abstract: Vesicular glutamate transporters (VGLUTs) allow the loading of presynaptic glutamate vesicles and thus play a critical role in glutamatergic synaptic transmission. Rose Bengal (RB) is the most potent known VGLUT inhibitor (Ki 25 nM); therefore we designed, synthesized and tested in brain preparations, a series of analogs based on this scaffold. We showed that among the two tautomers of RB, the carboxylic and not the lactonic form is active against VGLUTs and generated a pharmacophore model to determine the minimal structure requirements. We also tested RB specificity in other neurotransmitter uptake systems. RB proved to potently inhibit VMAT (Ki 64 nM) but weakly VACHT (Ki>9.7 microM) and may be a useful tool in glutamate/acetylcholine co-transmission studies.
authors: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR8601 CNRS, Université Paris Descartes, 45 rue des Saints-Pères, 75270 Paris 06, France.
authors: Nicolas
authors: N
authors: Pietrancosta
authors: Albane
authors: A
authors: Kessler
authors: Franck-Cyril
authors: FC
authors: Favre-Besse
authors: Nicolas
authors: N
authors: Triballeau
authors: Thomas
authors: T
authors: Quentin
authors: Bruno
authors: B
authors: Giros
authors: Salah
authors: S
authors: El Mestikawy
authors: Francine C
authors: FC
authors: Acher
mesh_terms: D000818:Animals; D008956:Models, Chemical; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D012395:Rose Bengal / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D050496:Vesicular Glutamate Transport Proteins; D012395:Rose Bengal