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By characterizing the binding of these toxins to neuronal membranes, we show that they have more potent effects as positive allosteric modulators (PAMs) of insect nicotinic acetylcholine receptors (nAChRs), consistent with their neuroexcitatory toxicology. Alanine scanning analysis of \u03c9\u2010hexatoxin\u2010Hv1a reveals a structure\u2013activity relationship for binding that mirrors that for insecticidal activity. Spinosyn A does not compete with \u03c9\u2010hexatoxin\u2010Hv\u20101a for binding, and we show that these two PAMs have distinct pharmacology of binding indicating that they act at different receptor populations. 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