Effect of sigma ligands on the cocaine-induced convulsions in mice

It has been hypothesized that some of negative effects exerted by cocaine are mediated via sigma (sigma) receptors. This report demonstrates the effects of selective sigma ligands, panamesine, DTG, rimcazole and SA 4503, on the cocaine-induced convulsions in mice and locomotor hyperactivity in rats. Only panamesine decreased both these effects of cocaine, whereas DTG and rimcazole increased the total time of cocaine-evoked convulsions and locomotor activity. SA 4503 slightly enhanced and prolonged cocaine-induced convulsions but it was ineffective in locomotor hyperactivity test. Moreover, the increase in cocaine-induced locomotor hyperactivity evoked by DTG was antagonized by panamesine. The obtained results indicate that panamesine, a selective sigma ligand with a preference for sigma1 receptor subtype and potential antagonistic activity, decreased the effects of cocaine. DTG and rimcazole (potential sigma1/sigma2 sites agonists) as well as SA 4503 (potential sigma1 site agonist) showed rather opposite effects. These findings support the idea that sigma2 receptor subtype is involved in psychomotor stimulant effects of cocaine while sigma1 receptor subtype participates in the cocaine-induced convulsions. In addition, sigma receptor antagonists (especially sigma1 ones) are able to antagonize toxic effects of cocaine while sigma agonists facilitate them.