Tropisetron is widely regarded as a potent and selective 5-HT3 antagonist used to treat nausea and emesis in cancer patients undergoing radiation and chemotherapy. Recently, it has been demonstrated that tropisetron may also be an agonist for the α7 nAChR. Tropisetron exhibited high affinity binding for α7 nAChRs labeled with [3H]-methyllycaconitine (MLA) and evoked electrophysiological responses in primary rat hippocampal neurons that were blocked by MLA in the low nanomolar concentration range (Cortes-Burgos et al., SFN, 2001). To explore the potential role of tropisetron as an α7 nAChR agonist in the retina, we have investigated the neuroprotective effect of tropisetron on glutamate-induced excitotoxicity in cultured adult pig retinal ganglion cells (RGCs) isolated through a “panning” technique. In this model system, glutamate-induced excitotoxicity (500 μM) was eliminated in the presence of 5 μM ACh. Blockade of this effect with α-bungarotoxin (α-BTX) and MLA indicate an α7 nAChR-dependent mechanism (W...