We have examined the partitioning/transfer of the Ca2+ antagonist flunarizine from the aqueous phase into phospholipid bilayers. We show that the binding of the cationic amphiphilic drug flunarizine to phospholipid bilayers displays traditional linear concentration-dependent characteristics once unmasked of electrostatic effects. The coefficient for the binding/partitioning of flunarizine to phosphatidylcholine was found to be 28700 M-1, supporting the notion that this drug may be particularly membrane-active. The thermodynamics of the partitioning/transfer process have also been studied using high-sensitivity titration calorimetry. Binding was found to be predominantly enthalpy-driven with only a small entropic contribution; delta H = -22.1 kJ.mol-1 (-5.3 kcal.mol-1) at 27 degrees C. This is in conflict with established ideas of entropy-driven partitioning of drugs into phospholipid membranes as a result of the ‘hydrophobic effect’. The strong enthalpic nature of binding is interpreted as being indicative of strong lipophilic interactions between the drug and the phospholipid phase.
Research Article| April 15 1993
Binding of the calcium antagonist flunarizine to phosphatidylcholine bilayers: charge effects and thermodynamics
P G Thomas;
Biochem J (1993) 291 (2): 397–402.
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P G Thomas, J Seelig; Binding of the calcium antagonist flunarizine to phosphatidylcholine bilayers: charge effects and thermodynamics. Biochem J 15 April 1993; 291 (2): 397–402. doi: https://doi.org/10.1042/bj2910397
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