The polyamine synthesis inhibitor alpha-difluoromethylornithine is neuroprotective against N-methyl-D-aspartate-induced brain damage in vivo.
We examined the ability of alpha-difluoromethylornithine (DFMO), an inhibitor or ornithine decarboxylase, the rate limiting enzyme for polyamine biosynthesis, to protect the brain of the perinatal rat from N-methyl-D-aspartate (NMDA)-induced brain damage. Treatment of the rat pups with DFMO administered either by i.p. injection (500 mg/kg x 2) or through the milk of the mother (2% solution in mother's drinking water) significantly reduced, by 48 and 62%, respectively, the brain damage produced by intrastriatal NMDA injection. We conclude that activation of polyamine synthesis may mediate part of the neurotoxic action of NMDA.
Kish
S J
SJ
Department of Pharmacology, University of Toronto, Ontario, Canada.
Wilson
J M
JM
Fletcher
P J
PJ
D000818:Animals; D015317:Biogenic Polyamines / Q000096:biosynthesis*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000518:Eflornithine / Q000627:therapeutic use*; D008954:Models, Biological; D016202:N-Methylaspartate; D051381:Rats
D015317:Biogenic Polyamines; D016202:N-Methylaspartate; D000518:Eflornithine