We found a potent and selective sigma 1 (sigma 1) receptor ligand, SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride). This compound had a high affinity for sigma 1 receptor subtype (IC50 = 17 +/- 1.9 nM), but a low affinity for sigma 2 receptor subtype (IC50 = 1800 +/- 310 nM). The present study examines the effect of this compound on the central cholinergic functions, since sigma receptor has been reported to interact with the central cholinergic neurons. SA4503 elicited the increase in extracellular acetylcholine level in rat frontal cortex, while it did not affect the striatal acetylcholine level. On the other hand, tetrahydroaminoacridine (THA), an acetylcholinesterase (AChE) inhibitor, increased the extracellular acetylcholine level in both regions. Although both compounds had anti-amnesic effect against scopolamine-induced memory impairment, THA also induced catalepsy in rats. These results suggest that SA4503 may be a novel cognitive enhancer, with sigma 1 receptor agonistic properties. In addition, SA4503 does not cause striatal cholinomimetic side-effects, which is different from THA.