Correlation between the plasma concentration of mepirodipine and its occupancy of Ca2+ antagonist receptors in rats.
The relationship between the plasma concentration of mepirodipine (1,4-dihydropyridine Ca2+ antagonist) and its occupancy of cardiac and cerebral Ca2+ antagonist receptors in rats has been characterized by a radioreceptor assay technique using (+)-[3H]PN 200-110. Oral administration of mepirodipine in rats produced a dose-dependent and sustained decrease in the number of specific (+)-[3H]PN 200-110 binding sites in both tissues, and the effect was more pronounced in the cardiac tissue than in the cerebral cortex. The occupancy of cardiac and cerebral Ca2+ antagonist receptors by mepirodipine correlated well with its plasma concentration, whereas a 20-fold higher plasma concentration of this drug was necessary to occupy Ca2+ antagonist receptors in the cerebral cortex. Thus, these data suggest that mepirodipine occupies Ca2+ antagonist receptors in cardiovascular tissue selectively over those in brain tissue.
Yamada
S
S
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Matsuoka
Y
Y
Kimura
R
R
D000818:Animals; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D017275:Isradipine / Q000493:pharmacokinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D015220:Calcium Channels; C050699:mepirodipine; D009543:Nifedipine; D017275:Isradipine