The pyrimido-pyrimidine derivative RA-642 protects from brain injury in a combined model of permanent focal ischemia and global ischemia reperfusion.
The effects of pyrimido-pyrimidine derivatives (dipyridamole, RA-642 and mopydamole) on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation via the formation of hydroxyl anions. The antiperoxidative effect of RA-642 (in the microM range) was 10 times more potent than that of dipyridamole. Mopydamole did not exert any inhibitory effect on MDA production. In a model of ischemia reperfusion with bilateral occlusion of the common carotid arteries for 1 h and restoration of circulation for a period of 2 h, dipyridamole inhibited FeAs-induced MDA production but did not protect from postischemic brain tissue damage (measured by mitochondrial reduction of tetraphenyl tetrazolium). RA-642 inhibited FeAs-induced MDA production and showed 50-67% protection from tissue damage as compared with untreated animals, while mopydamole did not inhibit MDA production and showed 30-48% protection. No correlation was found between inhibition of lipid peroxidation and protection from brain tissue damage.
De La Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
Villalobos
M A
MA
Carrasco
T
T
Smith-Agreda
J M
JM
Sánchez de la Cuesta
F
F
D000818:Animals; D001921:Brain / Q000098:blood supply*; D004176:Dipyridamole / Q000494:pharmacology; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009012:Mopidamol / Q000494:pharmacology; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D013778:Tetrazolium Salts
D011743:Pyrimidines; D013778:Tetrazolium Salts; C011314:neotetrazolium; D009012:Mopidamol; C010650:RA 642; D004176:Dipyridamole