Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.

GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] has been described as a non-competitive AMPA (non-NMDA glutamate) receptor antagonist. In the present paper some behavioral effects of GYKI 52466 were studied in male Wistar rats and male Albino Swiss mice. GYKI 52466 reduced the locomotor activity in normal rats and mice, without evoking any symptoms of behavioral stimulation. The CGP 37849-induced hyperlocomotion was increased by GYKI 52466. The akinesia in monoamine-depleted rats was not affected by the drug studied. The antiakinetic effect of L-DOPA was not changed by GYKI 52466, whereas the antiakinetic effect of L-DOPA+CGP 37849 was decreased. GYKI 52466 increased the hyperlocomotion induced by apomorphine or cocaine. The drug did not change the catalepsy induced by haloperidol or fluphenazine, as well as the anticataleptic effect of CGP 37849. GYKI 52466 was inactive in the forced swimming test, but increased the antidepressant effect of CGP 37849. The flexor and extensor muscle tone of the rats hind limb was not modified by GYKI 52466. The results obtained indicate that GYKI 52466 shows a neuropharmacological profile similar but not identical with that of the quinoxalines (competitive AMPA receptor antagonists) studied previously.