Platelet activating factor antagonists interact with GABA(A) receptors

Platelet activating factor (PAF) is ubiquitous in mammals, and may have multiple functions in the central nervous system. Triazolobenzodiazepine compounds are active both at the GABA(A) receptor and as PAF antagonists. To investigate whether PAF antagonist activity is involved in the actions of triazolobenzodiazepines, we examined effects of two nonbenzodiazepine PAF antagonists on binding and function at the GABA(A) receptor. The gingkolide terpene, BN 52021 and the dioxolane-based compound BN 52115 had no effect on benzodiazepine binding or chloride channel binding in cortical membrane preparations. However, chloride uptake into cortical synaptoneurosomes was enhanced with 1 uM BN 52021 but not 1 uM BN 52115. The effect of BN 52021 was prevented by 1 uM flumazenil. PAF antagonists appear to augment GABA(A) receptor function without affecting binding.