Cocaine interacts with sigma receptors at physiologically relevant concentrations. While earlier studies demonstrate that antagonism of sigma(1) receptors attenuates the behavioral actions of cocaine, the contribution of sigma(2) receptors is unclear. Therefore, in the present study, 3 alpha-tropanyl-2-(4-chlorophenoxy)butyrate ((+/-)-SM 21), a compound with high and preferential affinity for sigma(2) receptors, was tested for its ability to attenuate cocaine-induced behaviors. Pre-treatment of Swiss Webster mice with (+/-)-SM 21 significantly attenuated cocaine-induced convulsions and locomotor activity.