Rose Bengal analogs and vesicular glutamate transporters (VGLUTs)

Bioorg Med Chem. 2010 Sep 15;18(18):6922-33. doi: 10.1016/j.bmc.2010.06.069. Epub 2010 Jun 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Models, Chemical
  • Models, Molecular
  • Rats
  • Rats, Sprague-Dawley
  • Rose Bengal / analogs & derivatives*
  • Rose Bengal / chemistry
  • Rose Bengal / pharmacology
  • Structure-Activity Relationship
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / metabolism
  • Vesicular Glutamate Transport Proteins / antagonists & inhibitors*
  • Vesicular Glutamate Transport Proteins / metabolism


  • Vesicular Glutamate Transport Proteins
  • Rose Bengal