Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex

Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex, was studied in male Albino-Swiss mice. SL 82.0715, in doses which given alone were inactive in electroshock-induced seizures, potentiated the anticonvulsant effects of CGP 37849. In normal mice, SL 82.0715 decreased the spontaneous locomotor activity, did not affect the locomotor hyperactivity induced by MK-801 and attenuated CGP 37849-induced locomotor hyperactivity. The D-amphetamine locomotor hyperactivity was also antagonized by SL 82.0715. SL 82.0715 did not significantly change the locomotor activity in monoamine-depleted mice (treated with reserpine + alpha-methyl-p-tyrosine). When administered together with clonidine, SL 82.0715 increased the locomotor activity in monoamine-depleted mice but this effect did not reach the level of statistical significance. SL 82.0715 did not change the locomotor activity induced by joint administration of clonidine and MK-801 or clonidine and CGP 37849, in monoamine-depleted mice. The locomotor hyperactivity evoked by L-DOPA (given jointly with benserazide) was not changed by SL 82.0715. SL 82.0715 had no effect on fluphenazine- and haloperidol-induced catalepsy in mice. CGP 37849 attenuated catalepsy induced by haloperidol; that effect was not changed by SL 82.075. The studied compound did not affect the immobility time and had no effect on the action of MK-801 or CGP 37849 in the forced swimming test. The obtained results indicate that SL 82.0715 has a different pharmacological profile than other NMDA antagonists (at least MK-801 and CGP 37849). SL 82.0715 does not increase behavioral actions of MK-801 and CGP 37849, potentiating anticonvulsant effect of CGP 37849 only.