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

Synthesis of octyl-O-beta-D-mannopyranoside, a caloporoside analogue was ac hieved by the activation of 2,3,4,6-tetra-O-benzyl-1-O-1',3'2'-dioxaphospha cyclohexane-alpha,beta-D-mannopyranosyl-2-oxide with TMSOTf (Trimethyl sily l triflate) and subsequent debenzylation. At 100 mu M the molecule signific antly 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 proposa ls that such molecules bind to the TBPS (tert-Butylbicyclophosphorothionate ) site to block the chloride channel. (C) 2000 Elsevier Science Ltd. All ri ghts reserved.