P01 - Characterization of nicotinic acetylcholine receptor modulators with a focus on bispyridinium compounds as possible treatments for organophosphate poisoning
nAChR-mediated effects, such as impairment of neuromuscular junctions and respiratory failure constitute a therapeutic gap in the treatment of organophosphate poinsoning (e.g. tabun, soman, or the OPC pesticide
fenamiphos). Positive allosteric modulators (PAMs) that inhibit nAChR desensitization represent a promising therapeutic approach. In the proposed project we will use a combination of electrophysiology, mutagenesis, and computer simulations to determine the binding site and molecular mode of action of selected modulatory substances at human
nAChR subtypes and thus provide a basis for the development of improved compounds for the treatment of organophosphate poisoning.