ucb 11056, a new potential nootropic drug, amplifies induced cyclic AMP formation in rat brain tissue.
ucb 11056 [2-(4-morpholino-6-propyl-1,3,5-triazin-2-yl)aminoethanol] induced a significant (approximately 25%) increase in cyclic AMP levels in different brain areas following its intraperitoneal injection. This effect started as early as 2 min postinjection and lasted for 30 min, after which cyclic AMP levels returned to normal. In hippocampal slice preparations in vitro, ucb 11056 exerted a strong potentiation of cyclic AMP levels when it was combined with agents such as norepinephrine, forskolin, and isoproterenol. Only a slight effect on cyclic AMP levels was measured when ucb 11056 was incubated alone with hippocampal slices. The potentiating effect of ucb 11056 on norepinephrine-stimulated cyclic AMP formation was partially reduced when slices were pretreated with yohimbine and totally abolished when slices were treated with propranolol. These combined data indicate that (a) ucb 11056 rapidly increases cyclic AMP levels in the rat brain in vivo and (b) ucb 11056 potentiates stimulated cyclic AMP formation in vitro. The data also suggest that the central effect of ucb 11056 might be via the modulation of cyclic AMP generation, most probably mediated through adenylate cyclase activation mechanisms combined with a weak inhibitory activity on the cyclic nucleotide phosphodiesterase activity.
el Tamer
A
A
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Raikoff
K
K
Corey
J
J
Wülfert
E
E
Hanin
I
I
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D009025:Morpholines; D011619:Psychotropic Drugs; D014227:Triazines; C084361:2-(4-morpholino-6-propyl-1,3,5-triazin-2-yl)aminoethanol; D005576:Colforsin; D015016:Yohimbine; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol