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-arylalky lindol-3-ylglyoxylylamide derivatives, which have recently been characteriz ed as partial agonists at central benzodiazepine binding sites, to prevent the rat cardiac mitochondrial alterations resulting from acute loud noise e xposure. In particular, we evaluated the effects of these new compounds on the ultrastructural damage induced by noise stress an 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 obser ved a cardioprotective effect which was more marked after 6 hr compared wit h 12 hr of noise exposure. Confirming our recent data showing that full ago nists 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 bindi ng studies, the protective activity seems to be related more to their actio n at central than at: peripheral benzodiazepine receptors.