Amiodarone-liposome interaction: a multinuclear NMR and X-ray diffraction study.
Amiodarone, a potent antiarrhythmic drug, is widely used in cardiology. Its electrophysiological effects, as well as many of its side effects, seem to involve lipids. We report here a multinuclear NMR and X-ray diffraction study of amiodarone in egg phosphatidylcholine liposomes and lipid multilayers. In proton NMR experiments, amiodarone alters the signal from the lipid trimethyl ammonium group for pH values ranging from 3.2 to 8.4; cholesterol does not cause this alteration. The addition of SCN- changes both the proton and phosphorus NMR spectra of liposomes containing amiodarone. For both proton and carbon NMR, amiodarone modifies the signal from the lipid methylene groups, but to a far lesser extent than does cholesterol. Incorporation of amiodarone in EPC bilayers also modifies the low-angle X-ray diffraction patterns, decreasing the lamellar repeat period at low water contents, but swelling the fluid spaces between bilayers at high water contents. Electron density profiles and modeling studies using the X-ray data indicate that amiodarone decreases the bilayer thickness and adds electron density at the interfacial region of the bilayer. Our analysis of the NMR and X-ray data indicates that the iodine atoms of amiodarone are located near the hydrocarbon/water interface and that the tertiary amine of amiodarone is in the headgroup region of the bilayer.
Jendrasiak
G L
GL
Department of Radiation Oncology, East Carolina University, Greenville, NC 27858-4354.
McIntosh
T J
TJ
Ribeiro
A
A
Porter
R S
RS
D000638:Amiodarone; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol; D006863:Hydrogen-Ion Concentration; D017879:Isothiocyanates; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D013861:Thiocyanates; D014961:X-Ray Diffraction
D017879:Isothiocyanates; D008081:Liposomes; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D013861:Thiocyanates; C037152:isothiocyanic acid; D002784:Cholesterol; D000638:Amiodarone