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.