Open AccessNeuroprotective Effect of YM-39558, Orotic Acid Ethylester, in Gerbil Forebrain Ischemia
Author(s) -
Hiraku Akiho,
Akihiko Iwai,
Mika Katoh-Sudoh,
Shinichi Tsukamoto,
Kazuo Koshiya,
Tokio Yamaguchi
Publication year - 1998
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.76.441
Subject(s) - orotic acid , gerbil , neuroprotection , ischemia , chemistry , hippocampal formation , pharmacology , biochemistry , forebrain , endocrinology , medicine , biology , central nervous system
We studied the effects of orotic acid and YM-39558 (2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid ethyl ester), orotic acid ethylester, on delayed neuronal death of hippocampal CA1 neurons induced by transient forebrain ischemia. Our data indicated that YM-39558 had high permeability across the blood brain barrier and was hydrolyzed to orotic acid, the active substance, in the brain. The neuronal damage was reduced significantly in animals intraperitoneally treated with YM-39558 (100 mg/kg x 3) after ischemia, but not with orotic acid in the same way. The results also suggested that the maintenance of a few ten micromolar orotic acid in cerebrospinal fluid were needed for its neuroprotective effects.