S. Ono et al., STUDIES ON COGNITIVE ENHANCING AGENTS .1. ANTIAMNESTIC AND ANTIHYPOXIC ACTIVITIES OF 2-DIMETHYLAMINOETHYL ETHERS AND RELATED-COMPOUNDS, Chemical and Pharmaceutical Bulletin, 43(9), 1995, pp. 1483-1487
N-(2-Dimethylaminoethyl)carboxamide (1a-d), 2-dimethylaminoethyl alkyl
ether (2a,b), and 2-dimethylaminoethyl 2-hydroxy-2-phenethyl ether (3
a-c) and its amino and methylene analogues (3d, 4) have been screened
for antiamnestic and antihypoxic activities in mice. A clear reversing
effect on electroconvulsive shock-induced amnesia was found with 1a-d
, 2a,b, and 2-dimethylaminoethyl 2-hydroxy-2-phenylethyl ether (3a). H
owever, a protective effect against hypoxia was only observed with 3a.
Compound 3a, which displayed the dual activity, was further investiga
ted for ameliorating effect on CO2-induced memory impairment, and it w
as found to be more potent than indeloxazine and bifemelane. In additi
on, the acute toxicity of 3a in mice was significantly lower than that
of tacrine, but its serum-to-brain penetration ability in rats was le
ss than that of the reference drugs.