The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jan 1996
Comparative StudyBinding of bupivacaine to human serum proteins, isolated albumin and isolated alpha-1-acid glycoprotein. Differences between the two enantiomers are partly due to cooperativity.
Binding parameters of R(+)- and S(-)-bupivacaine were determined for human serum proteins, human alpha-1-acid glycoprotein (AAG) and human serum albumin (HSA), using ultrafiltration. Binding parameters were estimated according to the Scatchard model of the law of mass action using nonlinear regression. A sigmoid (cooperativity) term was added when needed. ⋯ S(-) and R(+) enantiomers exhibited different behavior toward purified AAG and HSA due in part to complex allosteric cooperativity (positive or negative depending on the ligand/protein ratio). In conclusion, we observed stereoselective binding of bupivacaine to AAG and HSA. Moreover, cooperativity occurred, and the behavior of the two enantiomers showed marked differences in this respect.