Quaternary ammonium anticholinesterases have different effects on nicotinic receptors: is there a single binding site?

Copious current research is devoted to finding new modulators of nicotine acetylcholine receptors (nAChRs), in view of their high relevance for nervous system physiology and because alterations in their number and/or function are related to several neurological disorders and neurodegenerative diseases (Pereira et al., 2002). Recently, we have shown that 1,5-bis(4-allyldimethyl ammonium phenyl) pentan-3-one dibromide (BW284c51), a quaternary ammonium cholinesterase inhibitor (QChEI), selectively inhibits nicotinic currents (IACh) by blocking the nAChR channel (Olivera et al., 2005). Interestingly, we found different effects of BW284c51 on nAChRs from those described previously for other QChEIs (Bertrand et al., 1992; Yost and Maestrone, 1994), such as decamethonium and edrophonium. Therefore, this work was aimed at characterizing, comparing, and elucidating the mechanisms underlying the action of different QChEIs on nAChRs.