STUDIES ON COGNITIVE ENHANCING AGENTS .1. ANTIAMNESTIC AND ANTIHYPOXIC ACTIVITIES OF 2-DIMETHYLAMINOETHYL ETHERS AND RELATED-COMPOUNDS

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.