As part of our studies to discover P2X 7 receptor antagonists, the sponge Callyspongia sp. was investigated. A new tripyridine alkaloid niphatoxin C ( 1) was isolated and had P2X 7 receptor antagonism; however, cytotoxicity of THP-1 cells was the predominant biological effect at higher concentrations. Its structure was determined by 1- and 2-D NMR spectroscopy.