Relationship between hyperammonemia and dementia

• Published in: Japanese Journal of Pharmacology Vol. 64; no. suppl.2; p. 352
• Main Authors: Ito, Rieko, Matsuoka, Yutaka, Sunagane, Nobuyoshi, Uruno, Tsutomu, Kubota, Kazuhiko
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1994
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)51042-3

Effects of methionine sulfoximine (MSO) , an inhibitor of glutamate syn-thetase, and urease on blood ammonialevel and learning ability were stud-ied. An i.p. administration of MSO ( 100 mg/kg) signficantly impaired learning ability in the active avoid-ance test and significantly elevated blood ammonia and blood urea nitrogen levels in rats fed with a protein-rich diet. In mice, repeated administration of MSO (25 mg/kg i.p. every other day) or urease (480 unit/kg s.c. every other day) significantly impaired learning ability in Morris's water maze test. Urease elevated ammonia level, but MSO did not. Hyperammonemia has been known to cause glutamate release in CNS. Pretreatment with MK-801 ( 1 mg/kg i. v, ) , a non-competitive antagonist of the NMDA- type glutamate receptor, significantly decreased MSO-induced convulsion in mice. The refore , learn-ing impairment induced by MSO and urease may be concerned with the gluta-mate kinetics in CNS.