PubMed · 14780289
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P MORROW, J R SCHENKEN. 1950. Nupercaine poisoning.. https://pubmed.ncbi.nlm.nih.gov/14780289/
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Interaction of the local anesthetic dibucaine with small unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) and dioleoylphosphatidylcholine (DOPC) containing different mole percents of monosialoganglioside (GM1) has been studied by fluorescence spectroscopy. Fluorescence measurements on dibucaine in the presence of phospholipid vesicles containing various amounts of GM1 yielded a pattern of variation of wavelength at emission maximum and steady-state anisotropy which indicated that the microenvironment of dibucaine is more hydrophobic and rigid in membranes that contain GM1 than in membranes without it. Experiments on quenching of fluorescence from membrane-associated dibucaine by potassium iodide showed reduced quenching efficiency with the increase in GM1 content of the vesicles, demonstrating lesser accessibility of the iodide quenchers to dibucaine in the presence of GM1, when compared to that in its absence. Total emission intensity decay profiles of dibucaine yielded two lifetime components of approximately 1 and approximately 2.8-3.1 ns with mean relative contributions of approximately 25 and approximately 75%, respectively. The mean lifetime in vesicles was 20-30% lower than in the aqueous medium and showed a definite increase in presence of GM1 from that in the absence of it. All the spectral properties point that dibucaine encountered regions of membrane containing significant amount of GM1 and penetrated deeper in hydrophobic core of the bilayer.
Steady-state and time-resolved fluorescence data are reported for the local anesthetic dibucaine in the absence and presence of phospholipid vesicles. These vesicles were comprised of dimyristylphosphatidyl choline and approximately 10% dimyristylphosphatidyl glycerol. Solute quenching studies show the bound drug to be protected from collision with iodide ion. The fluorescence lifetime of dibucaine is not significantly changed upon binding to vesicles. The fluorescence anisotropy of dibucaine increases upon association with the vesicles. Anisotropy decay measurements show that the rotational correlation time, phi, of bound dibucaine is increased about one hundred fold over that for free dibucaine. This indicates that the rotational motion of bound dibucaine is slowed by its interaction with the phospholipids. However, we find no evidence that the rotational motion of bound dibucaine is anisotropic.
The therapeutical efficacy of PROCTOSEDYL (Rousel Ltd., France) was investigated in 25 pregnant women with chronic hemorrhoids. Excellent results, including elimination of clinical symptoms and good tolerability, were achieved in 100% of the cases by the local conservative treatment only, which makes Proctosedyl especially suitable for application during pregnancy.