SOME CENTRAL EFFECTS OF CGP-37849 AND CGP-39551, THE COMPETITIVE NMDARECEPTOR ANTAGONISTS - POTENTIAL ANTIPARKINSONIAN ACTIVITY

Two new competitive NMDA receptor antagonists with oral activity CGP 3 7849 (D,L-E-amino-methyl-phosphono-3-pentenoic acid) and its ethyl est er CGP 39551 were studied in rats. CGP 37849 did not change the locomo tor activity or increased it. The hyperactivity induced by CGP 37849 w as antagonized by haloperidol but not idazoxan or prazosin. CGP 39551 decreased the locomotor activity. The studied compounds did not increa se the locomotion in monoamine-depleted (pretreated with reserpine and alpha-methyl-p-tyrosine) rats. Clonidine induced antiakinetic effect in monoamine-depleted rats. This effect was more pronounced after join t administration of clonidine and CGP 37849 or CGP 39551. The locomoto r hyperactivity induced by joint dministration of CGP 37849 and clonid ine was inhibited by haloperidol but not prazosin or idazoxan. CGP 378 49 but not CGP 39551 also enhanced antiakinetic effect of L-DOPA (give n together with benserazide) in monoamine-depleted rats. CGP 37849 ant agonized the spiperone- and fluphenazine-induced catalepsy; CGP 39551 had considerably weaker antagonistic effect. The reserpine-induced cat alepsy was attenuated by CGP 37849. MK-801, a non-competitive NMDA ant agonist inhibited spiperone- but not reserpine-induced catalepsy. The obtained results indicate that CGP 37849 administered alone or in comb ination with L-DOPA or clonidine may be a potential anti-parkinsonian drug.