UCB 11056, A NEW POTENTIAL NOOTROPIC DRUG, AMPLIFIES INDUCED CYCLIC-AMP FORMATION IN RAT-BRAIN TISSUE

ucb 11056 rpholino-6-propyl-1,3,5-triazin-2-yl)aminoethanol] induced a significant (almost-equal-to 25%) increase in cyclic AMP levels in di fferent brain areas following its intraperitoneal injection. This effe ct started as early as 2 min postinjection and lasted for 30 min, afte r which cyclic AMP levels returned to normal. In hippocampal slice pre parations in vitro, ucb 11056 exerted a strong potentiation of cyclic AMP levels when it was combined with agents such as norepinephrine, fo rskolin, and isoproterenol. Only a slight effect on cyclic AMP levels was measured when ucb 11056 was incubated alone with hippocampal slice s. The potentiating effect of ucb 11056 on norepinephrine-stimulated c yclic AMP formation was partially reduced when slices were pretreated with yohimbine and totally abolished when slices were treated with pro pranolol. These combined data indicate that (a) ucb 11056 rapidly incr eases cyclic AMP levels in the rat brain in vivo and (b) ucb 11056 pot entiates stimulated cyclic AMP formation in vitro. The data also sugge st that the central effect of ucb 11056 might be via the modulation of cyclic AMP generation, most probably mediated through adenylate cycla se activation mechanisms combined with a weak inhibitory activity on t he cyclic nucleotide phosphodiesterase activity.