Isradipine (PN 200-110) is a highly potent calcium entry blocker with an asymmetrically substituted dihydropyridine ring (methyl- and isopropylester, respectively). The binding of the (+)-(S)-isradipine and (-)-(R)-isradipine to isolated human serum albumin (HSA, 30 mumol/l) and alpha 1-acid glycoprotein (AAG, 10 mumol/l) has been studied in vitro over a wide range of isradipine concentrations (0.06-20 mumol/l) using high-performance liquid chromatography (HPLC). HPLC experiments revealed that both isradipine enantiomers were bound to one class of high-affinity binding sites on the AAG molecule (n(S) = 0.83 +/- 0.05, Ka(S) = (1.33 +/- 0.25) x 10(6) l/mol, n(R) = 0.85 +/- 0.07, Ka(R) = (1.17 +/- 0.44) x 10(7) l/mol). The (R)-enantiomer also exhibited an interaction with the secondary low-affinity binding sites (n'Ka'(R) = (2.66 +/- 0.65) x 10(4) l/mol). In contrast, the pharmacologically more potent (+)-(S)-enantiomer was more strongly bound to HSA than its optical antipode (n(S) = 1.07 +/- 0.07, Ka(S) = (1.76 +/- 0.26) x 10(5) l/mol, nKa(R) = (3.62 +/- 0.06) x 10(4) l/mol). In general, the resulting binding characteristics of individual isradipine enantiomers showed stereoselectivity, but this was opposite for the two most important plasma binding proteins. The process of accumulation of isradipine by human platelets in the therapeutically relevant range (10-80 ng/ml) at 37 degrees C was devoid of stereoselectivity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.