A simple polar deacetylated caloporoside derivative is a positive modulator of the GABA(A) chloride channel complex in cortical mammalian neurones

Bioorg Med Chem Lett. 2000 Aug 7;10(15):1759-61. doi: 10.1016/s0960-894x(00)00330-9.

Abstract

Synthesis of octyl-O-beta-D-mannopyranoside, a caloporoside analogue was achieved by the activation of 2,3,4,6-rerra-O-benzyl-1-O-1',3'2'-dioxaphosphacyclohexane-a lpha,beta-D-mannopyranosyl-2-oxide with TMSOTf (Trimethyl silyl triflate) and subsequent debenzylation. At 100 microM the molecule significantly and reversibly increased the magnitude of GABA(A) currents evoked in cultured rat pyramidal neurones whilst concomitantly reducing the incidence of spontaneous synaptic activity. These results contradict earlier proposals that such molecules bind to the TBPS (tert-Butylbicyclophosphorothionate) site to block the chloride channel.

MeSH terms

  • Acetylation
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Chloride Channels / chemistry
  • Chloride Channels / drug effects*
  • Mannose / analogs & derivatives*
  • Mannose / chemistry
  • Mannose / pharmacology
  • Neurons / chemistry
  • Neurons / drug effects*
  • Rats
  • Salicylates / chemistry
  • Salicylates / pharmacology*
  • gamma-Aminobutyric Acid / chemistry
  • gamma-Aminobutyric Acid / drug effects*

Substances

  • Chloride Channels
  • Salicylates
  • caloporoside
  • gamma-Aminobutyric Acid
  • Mannose