Ascidians (sea squirts) contain a wealth of alkaloids, but their influence over neuronal nicotinic acetylcholine receptors (nAChRs) has not been evaluated. In this study, we examined the effects of two synthetic compounds, (−)-pictamine, a quinolizidine alkaloid from Clavelina picta, and (−)-lepadin B, a decahydroquinoline alkaloid from Clavelina lepadiformis, on major types of neuronal nicotinic receptors (α4β2 and α7) expressed in Xenopus oocytes. We found that these alkaloids are potent blockers at these receptors: acetylcholine-elicited currents through α4β2 and α7 receptors were blocked by (−)-pictamine with IC₅₀ values of 1.5 μM and 1.3 μM, respectively, and by (−)-lepadin B with IC₅₀ values of 0.9 μM and 0.7 μM, respectively. Interestingly, no recovery was observed after the removal of (−)-pictamine in oocytes expressing α4β2 receptors, whereas the inhibited α7 currents quickly recovered after the removal of (−)-pictamine. Since there are few compounds that elicit irreversible blocks of α4β2 receptors, (−)-pictamine will be a novel, valuable tool to remove the α4β2-nAChR action from neuronal activities mediated by these two major types of nAChRs.