The effects of the compound
SM-10888 (9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine citrate) in a number of pharmacological and biochemical tests were studied and compared to those of
tacrine (THA),
amiridin,
HP-029 and
physostigmine.
SM-10888 inhibited
cholinesterase activity (IC50: 2.3 x 10(-7) M) in rat cortical P2 fraction with almost the same potency as THA, while
SM-10888 was 2-4 times more potent than
amiridin and
HP-029, but about 10 times less potent than
physostigmine. When given to mice p.o.,
SM-10888 induced central (
hypothermia) and peripheral (salivation)
cholinergic effects. When the ratio of the ED50 value for
hypothermia to that for salivation was regarded as the index of the selectivity to the central nervous system (CNS),
SM-10888 was shown to be about 3 times more selective to the CNS than the other four drugs in mice. The minimum effective dose of
SM-10888 for its increasing effect on
acetylcholine (ACh) content in the mouse cerebral cortex was about 10 times higher than that of
physostigmine, but 5-10 times lower than those of THA,
amiridin and
HP-029. These results suggest that
SM-10888 is an adequate
drug for increasing the brain ACh content with less peripheral
cholinergic side effects than THA,
amiridin,
HP-029 and
physostigmine.