Chlorpromazine interaction with phosphatidylserines: a (13)C and (31)P solid-state NMR study.

Chlorpromazine (CPZ), a cationic, amphiphilic phenothiazine derivative is widely used as an antipsychotic drug because it antagonizes dopaminergic receptors. (13)C and (31)P solid-state NMR techniques were employed on phospholipid bilayers with and without CPZ. Phosphatidylserine from pig brain (PBPS), 1-palmitoyl-2-oleoyl phosphatidylserine (POPS), synthetic 1,2-dipalmitoyl phosphatidylcholine (DPPC) and chlorpromazineHCl were used to make phospholipid bilayers containing two types of phospholipids: DPPC (60%)/PBPS (40%) as well as POPS and PBPS bilayers without and with 10% CPZ. CPZ is found to prefer binding to the phosphate of phosphatidylserine, but also binding to the carboxyl of the serine head group in the DPPC/PBPS/CPZ bilayer is present. (31)P-NMR spectra indicate an effect of acyl chain unsaturation on the anisotropic motion of the charged serine head group. This implies that the serine head group anisotropic motion is restricted by intermolecular rather than intramolecular effects. The degree of phospholipid acyl chain unsaturation determines part of the CPZ bilayer interaction. The PBPS bilayer has the 22:6 acyl chain at 34 mol% and the C(4)?C(5) group of this acyl appears to be a determinant for CPZ bilayer interdigitation.