Monoamine oxidase inhibitors prevent striatal neuronal necrosis induced by transient forebrain ischemia.
Seven days after 30 min of ischemia, neuronal necrosis was observed in the striatum. Pretreatment with type A monoamine oxidase (MAO-A) inhibitors, clorgyline and RS-8359 ((+)-4-(4-cyanoanilino)-7-hydroxycyclopenta (3,2-e) pyrimidine) decreased significantly the number of necrotic neurons and inhibited changes in the dopamine metabolite contents during and after transient ischemia. An MAO-B inhibitor, deprenyl also decreased the neuronal necrosis, but it inhibited only the changes in 3,4-dihydroxyphenylacetic acid (DOPAC) content after reperfusion. The results suggest that the activation of dopamine metabolism after transient ischemia was mainly mediated by MAO-A and partly by MAO-B and suggest a possible role of dopamine deamination by MAO in the development of ischemic neuronal necrosis.
Matsui
Y
Y
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Kumagae
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000037:antagonists & inhibitors; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009336:Necrosis; D009474:Neurons / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion; D012642:Selegiline / Q000494:pharmacology
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D009570:Nitriles; D011743:Pyrimidines; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; C059590:RS 8359; D003010:Clorgyline; D004298:Dopamine