A new stigmastane-type steroidal alkaloid, 4-acetoxy-plakinamine B (1), was isolated from the Thai sponge Corticium sp. The compound was subjected to the acetylcholinesterase inhibitory activity determination to reveal a high inhibitory activity (IC(50) 3.75+/-1.69 microM). The kinetics of enzyme inhibition showed a decrease in V(max), whereas K(m) was increased, thus suggesting an unusual mixed-competitive mode of inhibition. Compound 1 is the first steroidal alkaloid bearing a stigmastane skeleton ever been reported to exhibit such good potency in the acetylcholinesterase inhibition bioassay.