Stereoselective binding of a 2,3-benzodiazepine to human serum albumin. Effect of conformation on tofizopam binding.

The binding of Tofizopam enantiomers to human serum albumin has been investigated by ultrafiltration and affinity chromatography. In solution, Tofizopam molecules exist in two conformations which slowly interconvert into each other. Both conformers of (R)-Tofizopam have the same binding constant of 4.8 X 10(3) M-1. The binding of the (S)-enantiomer, however, depends on the conformation. The minor and major (S)-conformers were characterized by association constants of 2.3 X 10(3) and 15.1 X 10(3) M-1, respectively. Thus, the stereoselectivity of binding differs for the two conformations of the enantiomers. Kinetic parameters for the interconversion of conformations have been determined. Tofizopam displaces both bound diazepam and warfarin.