Studies on cognitive enhancing agents. I. 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 (3a-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). However, a protective effect against hypoxia was only observed with 3a. Compound 3a, which displayed the dual activity, was further investigated for ameliorating effect on CO2-induced memory impairment, and it was found to be more potent than indeloxazine and bifemelane. In addition, the acute toxicity of 3a in mice was significantly lower than that of tacrine, but its serum-to-brain penetration ability in rats was less than that of the reference drugs.
Ono
S
S
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Yamafuji
T
T
Chaki
H
H
Todo
Y
Y
Maekawa
M
M
Kitamura
K
K
Tai
M
M
Narita
H
H
D000647:Amnesia / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001812:Blood-Brain Barrier; D003460:Crystallization; D004123:Dimethylamines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004597:Electroshock; D005019:Ethyl Ethers / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000523:psychology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D004123:Dimethylamines; D005019:Ethyl Ethers; D018697:Nootropic Agents