Nilvadipine as a neuroprotective calcium entry blocker in a rat model of global cerebral ischemia. A comparative study with nicardipine hydrochloride.
The effects of two dihydropyridine type calcium entry blockers, nilvadipine and nicardipine hydrochloride (nicardipine), on the liberation of free fatty acids (FFAs) were investigated using an experimental model of global cerebral ischemia in rats, and were compared with their pharmacokinetic properties. Nilvadipine, but not nicardipine, at a dose of 100 micrograms/kg i.v., significantly attenuated the liberation of FFAs, particularly docosahexaenoic and arachidonic acid. Furthermore, the brain concentration of nilvadipine was higher than that of nicardipine after equivalent dosing. The results of the present study demonstrate that pharmacokinetic differences between these two calcium entry blockers might explain the difference in their pharmacological efficacy.
Takakura
S
S
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sogabe
K
K
Satoh
H
H
Mori
J
J
Fujiwara
T
T
Totsuka
Z
Z
Tokuma
Y
Y
Kohsaka
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003655:Decerebrate State; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D005230:Fatty Acids, Nonesterified; C035100:nilvadipine; D009529:Nicardipine; D009543:Nifedipine