Age-related changes in the uptake of calcium channel blockers by brain capillary endothelial cells and synaptosomal fractions.
The effects of aging on the uptake of calcium channel blockers through brain capillaries to brain parenchyma were investigated. Two different piperazine derivatives, flunarizine and 1-[bis(fluorophenyl)-methyl]-4-(2,3,4-trimethoxybenzyl)piperazine (abbreviated as KB-2796), were orally administered to young and aged rats. The concentrations of the blockers in plasma, endothelial cells of the brain capillaries and synaptosomal fractions of the three brain regions were determined by high-performance liquid chromatography. Flunarizine was more incorporated into brain tissues than KB-2796 in both young and aged rats. The uptake efficiency of KB-2796 from the circulation to the brain decreased more remarkably than that of flunarizine in aged rats. The partition coefficients between n-octanol and water indicated that KB-2796 was less hydrophobic than flunarizine. These results suggest that the uptake of the chemicals seems to be influenced by their hydrophobicity and the age of animals given.
Waki
H
H
Department of Biochemistry, Tokyo Metropolitan Institute of Gerontology, Japan.
Kon
K
K
Tanaka
Y
Y
Ando
S
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics*; D002196:Capillaries / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005444:Flunarizine / Q000493:pharmacokinetics; D008297:Male; D009994:Osmolar Concentration; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013574:Synaptosomes / Q000378:metabolism*
D002121:Calcium Channel Blockers; D010879:Piperazines; C052424:lomerizine; D005444:Flunarizine