Central effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in mice

Central effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, were studied in male Albino-Swiss mice. CGP 37849--at high doses only--increased the locomotor activity, while CGP 39551 decreased it. CGP 37849 and CGP 39551 did not change the locomotor activity, in monoamine-depleted mice (treated with reserpine + alpha-methyltyrosine). However, when administered together with clonidine, both those compounds produced a distinct hyperactivity. That antiakinetic effect was antagonized by haloperidol, but not by prazosin or idazoxan. In monoamine-depleted mice both the CGP compounds inhibited the locomotor hyperactivity evoked by apomorphine or L-DOPA (given jointly with benserazide). CGP 37849 antagonized the catalepsy evoked by fluphenazine, haloperidol, spiperone and reserpine. After CGP 39551 administration, a decreased muscle tension was observed, which rendered evaluation of the influence on catalepsy impossible. The obtained results (the antiakinetic effect, antagonized by haloperidol, and the anticataleptic effect) indicate that the NMDA receptor antagonists studied may act via an indirect activation of the dopamine system.