title: Neuroprotective activity of creatylglycine ethyl ester fumarate.
abstract: BACKGROUND
  We have recently shown neuroprotective activity of the creatine amides in the focal cerebral ischemia in rats on the 280 mg/kg administration. In the present study, neuroprotective properties of creatylglycine ethyl ester fumarate (CrGEt) in rats with focal cerebral ischemia were explored in a wide dosage range (30-280 mg/kg, intravenous and intragastric).
  
  
  METHODS
  Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO).
  
  
  RESULTS
  The CrGEt administration 30 minutes before and at the last 5 minutes of MCAO dose dependently attenuated cerebral ischemic damage on 35%-65%, reduced neurobehavioral deficits, led to high neuronal survival in ischemic rat brains. The neuroprotective activity of CrGEt was mediated by its following abilities: (1) normalize the energy metabolism in the ischemic brains, maintaining adenosine triphosphate levels, and reducing lactate concentration; (2) inhibit the ischemia-reperfusion-related oxidative stress as evidenced by the increased activity of superoxide dismutase and the reduced levels of malondialdehyde. CrGEt served as a substrate for creatine kinase and a partial agonist of N-methyl-D-aspartate receptors; this partly explains mechanism of its neuroprotective action.
  
  
  CONCLUSIONS
  In view of the previously mentioned results, CrGEt holds a promise as a compound for treatment of ischemic brain disorders.
authors.affiliation: Department of Science, CJSC Vertex, St Petersburg, Russia.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Veselkina
authors.affiliation: Department of Science, CJSC Vertex, St Petersburg, Russia. Electronic address: vmorozov@vertex.spb.ru.
authors.forename: Vasily A
authors.initials: VA
authors.lastname: Morozov
authors.affiliation: Department of General and Special Morphology, Research Institute of Experimental Medicine of the Russian Academy of Medical Sciences, St Petersburg, Russia.
authors.forename: Dmitrii E
authors.initials: DE
authors.lastname: Korzhevskii
authors.affiliation: Department of Biophysics, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Denis B
authors.initials: DB
authors.lastname: Tihonov
authors.affiliation: Department of Biophysics, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Oleg I
authors.initials: OI
authors.lastname: Barygin
authors.affiliation: Department of Science, CJSC Vertex, St Petersburg, Russia.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Isaeva
authors.affiliation: Department of Science, CJSC Vertex, St Petersburg, Russia.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Portsel
authors.affiliation: Department of Pathophysiology, Saint Petersburg State Medical University n.a. I.P. Pavlova, St Petersburg, Russia.
authors.forename: Timur D
authors.initials: TD
authors.lastname: Vlasov
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054333:Drug Partial Agonism; D004355:Drug Stability; D004734:Energy Metabolism / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005650:Fumarates / Q000378:metabolism / Q000494:pharmacology*; D006207:Half-Life; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D005650:Fumarates; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C579481:creatine glycine ethylic ether fumarate; D019344:Lactic Acid; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D003402:Creatine Kinase
keywords: Creatine derivatives; cerebral ischemia; neuroprotection; neuroprotective activity