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

Abstract

Synthesis of octyl- O-β- d-mannopyranoside, a caloporoside analogue was achieved by the activation of 2,3,4,6- tetra- O-benzyl-1- O-1′,3′2′-dioxaphosphacyclohexane-α,β- d-mannopyranosyl-2-oxide with TMSOTf (Trimethyl silyl triflate) and subsequent debenzylation. At 100 μM 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.