%0 Journal Article %A KEISUKE KITAMURA %A HIDEKI KANO %A KEIJI YONEYAMA %A KEIICHIRO HOZUMI %T 1H Nuclear Magnetic Resonance Study on Transbilayer Permeation of Chlorpromazine in Lecithin Vesicles %D 1981 %J Molecular Pharmacology %P 124-127 %V 20 %N 1 %X Permeation of chlorpromazine across lecithin bilayers has been investigated by 1H NMR spectroscopy of lecithin vesicle solutions containing the shift reagents Pr3+ in the inside and Eu3+ in the outside aqueous phase of these vesicles, which were prepared by ultrasonication and ultrafiltration techniques. The 1H NMR spectrum of this sample showed that the choline methyl signal of the lecithin was split into two peaks, one signal arising from the internal monolayer shifted downfield by entrapped Pr3+ and the other to the external monolayer shifted to upfield by Eu3+. Addition of chlorpromazine hydrochloride to the sample reduced the lanthanide-induced shifts of both the internal and external choline methyl signals, due to the displacement of the lanthanide ions at the external and internal surfaces of the vesicle by the interaction of chlorpromazine with polar headgroups at both surfaces. The chlorpromazine interaction with the internal surfaces serves as a test of the transbilayer permeation of chlorpromazine. The addition of chlorpromazine also induced an upfield shift in the signal of the C-2 methylenes adjacent to the carbonyl groups in the fatty acid chains of the lecithin. This indicates that chlorpromazine molecules interacting with the external and internal surfaces insert their phenothiazine rings into the lecithin monolayers to such an extent that the C-2 methylene in the fatty acid chain could interact with the plane of the phenothiazine ring, the high field shift thus being induced by a magnetic anisotropy of the ring current. ACKNOWLEDGMENT The authors thank Dr. Y. Kuroda of Kyoto University for use of the HA-100D NMR spectrometer. %U https://molpharm.aspetjournals.org/content/molpharm/20/1/124.full.pdf