| Title | Drug-membrane interactions an example with the pair of anesthetic steroids alphaxalone and Δ16-alphaxalone | |
| Author | Thomas Mavromoustakos
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Vasileos Constantinou 48, Athens, 11635, Greece |
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| Citation | Mavromoustakos, T.: Drug-membrane interactions an example with the pair of anesthetic steroids alphaxalone and Δ16-alphaxalone, Epitheorese Klin. Farmakol. Farmakokinet. 12(3): 15-22 (1998) | |
| Publication Date | Received for publication: 10 September 1997
Accepted for publication: 20 October 1997 |
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| Full Text Language | English | |
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| Keywords | Phosphatidylcholine bilayers, anaesthetic steroids, dipalmitoyl phosphatidylcholine (DPPC), dimyristoyl phoshatidylcholine (DMPC), nuclear magnetic resonance (NMR), small angle x-ray diffraction, differential scanning calorimetry (DSC), cross polarization magic angle spinning (CP/MAS). | |
| Other Terms | review article | |
| Summary | This review article provides some experimental evidence using high resolution solid state NMR spectroscopy, small angle x-ray diffraction and differential scanning calorimetry which reveals differential effects between the two steroids alphaxalone and Δ16-alphaxalone in the membrane bilayers. To explain these differential effects a mechanism of action is proposed for these steroids which involves either direct action of these drugs on the phospholipid component of membranes or a lateral diffusion through the lipid bilayer and then action on a receptor site. These differential effects may account for their different biological activities. | |
| References | 1. Atkinson R.M., Davis B., Pratt M.A., Sharp H.M., Tomich E.G.: Action of some steroids on the central nervous system of the mouse. II. Pharmacology. J. Med. Chem. 8: 426 (1965)
2. Phillipps G.H.: Structure-Activity Relationships in steroidal anaesthetics. J. Steroid Biochem. 6: 607 (1975) 3. Davis J.H.: The description of membrane lipid conformation, order and dynamics by 2H-NMR. Biochim. Biophys. Acta 737: 117 (1983) 4. Fesik S.W., Makriyannis A.: Geometric Requirements for Membrane Perturbation and Anesthetic Activity. Conformational Analysis of Alphaxalone and Δ16-alphaxalone and 2H NMR Studies of Their Interactions with Model Membranes. Molecular Pharmacology, 27: 624: 629 (1985) 5. O’ Leary J.T., Ross P.D., Levin W.I.: Effects of Anesthetic and Nonanesthetic Steroids on Dipalmitoylphosphatidylcholine Liposome: A Calorimetric and Raman Spectroscopic Investigation.: Biochemistry 23: 4336 (1984) 6. Mavromoustakos T., Yang D.P., Makriyannis A.: Effects of the anesthetic steroid alphaxalone and its inactive Δ16-analog on the thermotropic properties of membrane bilayers. A model for membrane perturbation. Biochim. Biophys. Acta 1239: 257 (1995) 7. Mavromoustakos T., Yang D.P., Makriyannis A.: Topography of alphaxalone and Δ16-alphaxalone in membrane bilayers containing cholesterol. Biochim. Biophys. Acta 1194: 69 (1994) 8. Forbes J., Husted C., Oldfield E.: High-field, high-resolution proton “magic-angle” sample-spinning nuclear magnetic resonance spectroscopic studies of gel and liquid crystalline lipid bilayers and the effects of cholesterol. J. Am. Chem. Soc. 110: 1059 (1988) 9. Wu W.G., Chi L.M.: Comparisons of lipid dynamics and packing in fully interdigitated monoarachidoylphosphatidylcholine and non-interdigitated dipatmitoylphosphatidvlcholine bilayers: cross polarization/magic angle spinning 13C-NMR studies. Biochim. Biophys. Acta 1026: 225-235 (1990) 10. Earl W. L., VaanderHart D.L.: Observations in solid polyethylenes by C nuclear magnetic resonance with magic angle spinning. Macromolecules 12: 762 (1979) 11. Mavromoustakos T., Theodoropoulou E.t Yang D.P.: The use of high-resotution solid-state NMR spectroscopy and differential scanning calorimetry to study interactions of anaesthetic steroids with membrane. Biochim. Biophys. Acta 1328: 65-73 (1997) |
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| Relative Papers |
Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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