title: SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor.
abstract: The extracts of earth worms, Eisenia andrei, have been used as a therapeutic agent for stroke in the traditional medicine. It is also reported that the protease fraction separated from the extracts has strong anti-thrombotic activity. Besides anti-thrombotic actions, we found that SP-8203, N-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl]-N-{4-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino]butyl}acetamide, derived from the extracts of earth worms blocked N-methyl-(D)-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. The neuroprotective effects of SP-8203 were attributable to prevention of Ca(2+) influx through NMDA receptors. The systemic administration of SP-8203 markedly reduced neuronal death following middle cerebral artery occlusion in rats. SP-8203 significantly improved spatial learning and memory in the water maze test. These results provided strong pharmacological basis for its potential therapeutic roles in cerebral ischemia.
authors.affiliation: Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Noh
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Lee
authors.forename: Hyun Su
authors.initials: HS
authors.lastname: Hong
authors.forename: Chul Kyu
authors.initials: CK
authors.lastname: Lee
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: Cho
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
mesh_terms: D000081:Acetamides; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000378:metabolism / Q000517:prevention & control*; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology*
chemical_list: D000081:Acetamides; D018696:Neuroprotective Agents; D052999:Quinazolinones; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C552779:otaplimastat