Pharmacological action of YM737, a new glutathione analogue, in rats with experimental hematoma.
The effects of YM737, a glutathione analogue, and glutathione on neurological deficits and cerebral malondialdehyde concentrations were investigated in rats with experimental hematoma. A unilateral cerebral hematoma was provoked by injecting 0.25 ml of autologous blood around the capsula interna, putamen and caudate nucleus of the left cerebral hemisphere of the rat. Drugs were administered daily for four days beginning immediately after the operation. Neurological deficits and cerebral malondialdehyde concentrations were measured daily for 4 days. In the vehicle-treated group, deficits reached a maximum on the second day after the operation and then gradually recovered. YM737 (300 mg/kg, i.p.) accelerated recovery from neurological deficits, while glutathione had no effect. YM737 (300 mg/kg, i.p., on the fourth day after the operation) reduced the increase in malondialdehyde concentrations. Our results suggest that YM737 improves neurological deficits in this cerebral hematoma model, presumably partly due to inhibition of the lipid peroxidase response.
Yamamoto
M
M
Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Sakamoto
N
N
Iwai
A
A
D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006406:Hematoma / Q000188:drug therapy* / Q000503:physiopathology; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D008315:Malondialdehyde; C058293:glutathione monoisopropyl ester; D005978:Glutathione