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5. Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal and postischemic performance of the isolated rat heart

Author

Pantos, C. Mourouzis, I. Delbruyère, M. Malliopoulou, V. Tzeis, S. Cokkinos, D.D. Nikitas, N. Carageorgiou, H. Varonos, D. Cokkinos, D. Nisato, D.

Abstract

The present study investigated the effects of dronedarone and amiodarone on plasma thyroid hormones and the possible consequences on the response of the heart to ischemia. Amiodarone (30 mg/kg/day per os) or dronedarone (30 mg/kg/day per os) were administered for 2 weeks in normal and thyroxine-treated animals (25 μg/100 g body weight od sc, for 2 weeks), while animals without amiodarone and dronedarone served as controls. Isolated rat hearts were perfused in a Langendorff mode and subjected to 20 and 30 min of zero-flow global ischemia followed by 45 min of reperfusion. Functional changes were assessed by measuring left ventricular developed pressure (LVDP) under resting conditions and in response to ischemia-reperfusion, LVDP%, as well as the severity of ischemic contracture. Amiodarone resulted in increased T4, T4/T3 and rT3, whereas dronedarone did not alter the thyroid hormone profile in normal animals. In thyroxine-treated animals, amiodarone increased T4/T3 ratio but T4, T3 and rT3 levels were not altered. Basal functional parameters and ischemic contracture did not change by amiodarone and/or dronedarone neither in normal nor in thyroxine-treated hearts. In normal hearts, postischemic functional recovery, LVDP%, was not altered by amiodarone or dronedarone administration. LVDP% was statistically higher in thyroxine-treated hearts than in normal and this beneficial effect was not abolished by amiodarone or dronedarone treatment. © 2002 Elsevier Science B.V. All rights reserved.

Published
2002

6. Theoretical and experimental conformational analysis of two diastereomeric 'Val'-statine derivatives

Author

Toniolo, C., Valle, G., Marco Crisma, Bonora, G. M., Lelj, F., Cristinziano, P. L., Barone, V., Nisato, D., Toniolo, C, Valle, G, Crisma, M, Bonora, G. M., Lelj, F, Cristinziano, P. L., Barone, Vincenzo, and Nisato, D.

Subjects
Solutions, Magnetic Resonance Spectroscopy, X-Ray Diffraction, Protein Conformation, Molecular Sequence Data, Hydrogen Bonding, Stereoisomerism, Valine, Amino Acid Sequence, Amino Acids
Abstract

The preferred conformations and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 5-methylhexanoic acid ("Val"-statine) with (S,S) and (R,S) configurations at the 3-hydroxy and 4-amino carbon atoms, respectively, were determined in solution as well as in the crystal state by infrared absorption, 1H nuclear magnetic resonance and x-ray diffraction. A corollary conformational energy computation study was also carried out. In the crystal state intramolecular H-bonds are absent in both structures. However, the change in chirality of the carbon atom carrying the hydroxy group and the presence of a co-crystallized water molecule in the (S,S) isomer induce partially different backbone and "Val" side chain conformations and divergent intermolecular H-bonding schemes in the two isomers. A marked propensity to self-aggregate is seen in solvents of low polarity. The two isomers, however, are largely solvated in solvents of high polarity. Conformational energy computations indicate that in vacuo both diastereomers exhibit a significant flexibility and the conformers presenting absolute minima are not stabilized by any intramolecular bonding.

Published
1990

7. Synthesis and in vitro study of a diglyceride prodrug of a peptide

Author

Delie Salmon, Florence, Couvreur, P, Nisato, D, Michel, J B, Puisieux, F, and Letourneux, Y

Subjects
Renin/antagonists & inhibitors, Peptides/chemical synthesis, Chemical Phenomena, Chemistry, Physical, Hydrolysis, Molecular Sequence Data, Cesium, Diglycerides/chemical synthesis, Lipase, Buffers, In Vitro Techniques, Oligopeptides/chemical synthesis, Diglycerides, Solubility, Renin, Humans, Prodrugs, Amino Acid Sequence, Peptides, Prodrugs/chemical synthesis, Oligopeptides
Abstract

A diglyceride derivative of a pentapeptide renin inhibitor, the 1,3-dipalmitoyl-[Iva-Phe-Nle-Sta-Ala-Sta-acetyl]-glycerol was synthesized and tested in vitro as a potential prodrug for oral administration. The ability of the diglyceride analog to inhibit the renin activity was equivalent to that of the parent peptide after predigestion with pancreatic lipase. Furthermore, the presence of the palmitoyl groups was found to induce, in vitro, an efficient protection of the peptide from gastric and intestinal hydrolysis. During incubation with intestinal and gastric fluids, and with alpha-chymotrypsin and pancreatic lipase, the glycerolipidic derivative was more stable than the peptide alone. These results support the use of glycerolipidic prodrug for oral administration of peptides.

Published
1994

14. Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist.

Author

Serradeil-Le Gal, C, primary, Lacour, C, additional, Valette, G, additional, Garcia, G, additional, Foulon, L, additional, Galindo, G, additional, Bankir, L, additional, Pouzet, B, additional, Guillon, G, additional, Barberis, C, additional, Chicot, D, additional, Jard, S, additional, Vilain, P, additional, Garcia, C, additional, Marty, E, additional, Raufaste, D, additional, Brossard, G, additional, Nisato, D, additional, Maffrand, J P, additional, and Le Fur, G, additional

Published
1996
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19. ChemInform Abstract: A New Series of Imidazolones: Highly Specific and Potent Nonpeptide AT1 Angiotensin II Receptor Antagonists.

Author

BERNHART, C. A., primary, PERREAUT, P. M., additional, FERRARI, B. P., additional, MUNEAUX, Y. A., additional, ASSENS, J.‐L. A., additional, CLEMENT, J., additional, HAUDRICOURT, F., additional, MUNEAUX, C. F., additional, TAILLADES, J. E., additional, VIGNAL, M.‐A., additional, GOUGAT, J., additional, GUIRAUDOU, P. R., additional, LACOUR, C. A., additional, ROCCON, A., additional, CAZAUBON, C. F., additional, BRELIERE, J.‐C., additional, LE FUR, G., additional, and NISATO, D., additional

Published
1994
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