Effect of a new calcium antagonist (SM-6586) on experimental cerebral ischemia.
SM-6586 (SM) is a new derivative of dihydropyridine with potent calcium blocking activity and inhibitory activity of the Na+/H+ and Na+/Ca++ exchange transport. The effect of SM on survival rate, brain edema and metabolites was evaluated using two different models in spontaneously hypertensive rat (SHR). Global ischemia was induced by bilateral common carotid artery ligation (BLCL) and focal ischemia was induced by middle cerebral artery occlusion. The survival rate after BLCL was higher in the SM-treated group. The brain water content was lower, the ATP level was higher and lactate level was lower in the SM-treated group compared to the control group. In focal ischemia models, the SM-treated group showed a reduction of T1 relaxation time. The brain water content was significantly decreased in the SM-treated group. These results indicate that SM was effective in ameliorating the ischemic insult in global and focal cerebral ischemia models.
Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
F
F
Kashiwagi
Y
Y
Katayama
H
H
Igarashi
S
S
Iida
H
H
Muramatsu
A
A
Terashi
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D001929:Brain Edema / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014882:Water-Electrolyte Balance / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010069:Oxadiazoles; C075861:SM 6586