Nizofenone, a neuroprotective drug, suppresses glutamate release and lactate accumulation.
It was investigated whether nizofenone, 2'-chloro-2-(2-diethylaminomethyl-1- imidazolyl)-5-nitrobenzophenone fumarate, shows neuroprotective effect by inhibiting glutamate release and lactate accumulation in rats. Nizofenone (10 mg/kg i.p.) significantly inhibited neuronal cell death in the hippocampus CA1 pyramidal cells 7 days after 15 min of ischemia caused by 4-vessel occlusion. The extracellular level of glutamate and lactate increased in the hippocampus during ischemia. Upon reperfusion, the glutamate level decreased rapidly but, in contrast, the lactate level increased further and reached a maximum at 15 min following reperfusion. Nizofenone (10 mg/kg i.p.) completely inhibited the ischemic glutamate increase and post-ischemic lactate increase. These results suggest that the inhibition of ischemic release of glutamate and post-ischemic accumulation of lactate could contribute greatly to the neuroprotective effect of nizofenone.
Matsumoto
Y
Y
Yoshitomi Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Aihara
K
K
Kamata
T
T
Goto
N
N
D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy; D013050:Spectrometry, Fluorescence
D007093:Imidazoles; D007773:Lactates; D018696:Neuroprotective Agents; D019344:Lactic Acid; D018698:Glutamic Acid; C016910:nizofenone