Our previous studies demonstrated that
FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel antidementia
piperazine derivative, exerts beneficial effects on
memory deficits in various rodent models of
amnesia, through activation of the
somatostatin neuronal system. To extend the antiamnesic action of
FK960 to nonhuman primates,
FK960 was evaluated for its ability to reverse the deficits in visual recognition memory produced by
muscarinic cholinergic receptor blockade by
scopolamine or
N-methyl-D-aspartate receptor blockade by
dizocilpine (MK-801) in four rhesus monkeys performing a computer-automated version of delayed nonmatching to sample, with a list length of 20 trial-unique graphic symbols. Furthermore, the effects of
FK960 were compared with those of
physostigmine, a
cholinesterase inhibitor. Doses of
FK960 (1, 3.2, 10, 32,100, 320 or 1000 microg/kg) injected i.m. 30 min before testing minimally affected visual recognition memory when administered alone.
FK960 (1, 3.2, 10 or 32 microg/kg) significantly antagonized the deficits in visual recognition memory produced by
scopolamine (10 microg/kg); the same doses of the
drug minimally affected the deficits produced by
dizocilpine (32 microg/kg). Similarly,
physostigmine (3.2, 10 or 32 microg/kg) significantly and dose-dependently restored the visual recognition
memory deficits produced by
scopolamine (10 microg/kg) but not those produced by
dizocilpine (32 microg/kg). From these results, we conclude that
FK960 improves deficits in recognition memory associated with central
cholinergic hypofunction in nonhuman primates, and we suggest that the therapeutic potential of this
drug for patients with
dementia should be evaluated.