Synthesis and pharmacology of alkanediguanidinium compounds that block the neuronal nicotinic acetylcholine receptor.

Taking as models the polyamine toxin fraction FTX from the funnel-web spider venom, and the guanidinium moiety of guanethidine, a series of azaalkane-1, omega-diguanidinium salts were obtained. Some of them blocked ion fluxes through the neuronal nicotinic receptors for acetylcholine (nAChR). The blockade was exerted at submicromolar concentrations, suggesting a highly selective interaction with the nAChR. In fact, the active compounds on the nAChR ion channel did not recognize the voltage-dependent Na+ or Ca2+ channels of bovine adrenal chromaffin cells. Therefore, these compounds may be useful tools to clarify the functions of nAChR receptors in the central and peripheral nervous systems.