Effects of newly-developed benzodiazepine ligands on noise-induced mitochondrial damage in the rat

In this study we measured the ability of three newly-synthesized N-arylalkylindol-3-ylglyoxylylamide derivatives, which have recently been characterized as partial agonists at central benzodiazepine binding sites, to prevent the rat cardiac mitochondrial alterations resulting from acute loud noise e...

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Bibliographic Details
Published in:Annals of anatomy 2000-07, Vol.182 (4), p.311-318
Main Authors: Gesi, Marco, Pellegrini, Antonio, Lenzi, Paola, Da Settimo, Federico, Martini, Claudia, Salvetti, Francesca, Taliani, Sabrina, Fornai, Francesco
Format: Article
Language:English
Subjects:
Animals
Benzodiazepine ligands
Benzodiazepinones - pharmacokinetics
Benzodiazepinones - pharmacology
Binding, Competitive
Cardiotonic Agents - pharmacokinetics
Cardiotonic Agents - pharmacology
Heart
Heart Atria
Heart Ventricles
Isoquinolines - pharmacokinetics
Isoquinolines - pharmacology
Mitochondria
Mitochondria, Heart - drug effects
Mitochondria, Heart - metabolism
Mitochondria, Heart - pathology
Myocardium - pathology
Myocardium - ultrastructure
N-arylalkylindol-3-ylglyoxylylamide derivatives
Noise
Noise stress
Rat
Rats
Rats, Wistar
Receptors, GABA-A - metabolism
Stress, Psychological - metabolism
Stress, Psychological - pathology
Time Factors
Transmission electron microscopy
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Summary:In this study we measured the ability of three newly-synthesized N-arylalkylindol-3-ylglyoxylylamide derivatives, which have recently been characterized as partial agonists at central benzodiazepine binding sites, to prevent the rat cardiac mitochondrial alterations resulting from acute loud noise exposure. In particular, we evaluated the effects of these new compounds on the ultrastructural damage induced by noise stress on the right atrium and ventricle after 6 and 12 hr of loud noise exposure. In parallel experiments, we measured the affinity of these compounds for peripheral benzodiazepine binding sites. Following a single injection of the test products, we observed a cardioprotective effect which was more marked after 6 hr compared with 12 hr of noise exposure. Confirming our recent data showing that full agonists at benzodiazepine receptors produce cardioprotection, we demonstrate in this study that partial agonists, like indolylglyoxylylamides, can also produce a cardioprotective effect. Based on their greater affinity in binding studies, the protective activity seems to be related more to their action at central than at peripheral benzodiazepine receptors.
ISSN:0940-9602
1618-0402
DOI:10.1016/S0940-9602(00)80003-5