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Mitochondrial benzodiazepine receptors (MBRs) participate in many physiological processes, such as calcium flow regulation, proliferative and respiratory cell functions, mitochondrial steroidogenesis and adaptational reactions to stress. We have found that the selective anxiolytic gidazepam has a higher affinity for CNS MBRs as compared to central benzodiazepine receptors. The ability of gidazepam to bind to MBRs probably underlies a wide spectrum of its pharmacological effects. We have studied affinities of gidazepam analogs for CNS MBRs in search for the ligands possessing higher affinity and selectivity. The experiments were carried out with male Wistar rats weighing between 200-220 g. Affinities of the investigated compounds were assessed on their ability to displace radioligand Ro5-4864 from its specific binding sites on MBRs of rat brain. Within the series of tested compounds three substances comparable on affinity with Ro5-4864 were found. Experimental results have shown that the presence of chlorine atom in o-position of 5-phenyl substituent leads to a 10 to 15-fold increase in affinity for CNS MBRs. We have also found that the essential contribution in affinity of the investigated series is brought by lipophilicity of substituent in IN-position. Our data may be useful in design and synthesis of novel potent selectively acting ligands of CNS MBRs.

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Multi-membered N-heterocycles R 0690 Synthesis and Structure of 3-Arylidene and 3-Hetarylidene-1,2-dihydro--3H-1,4-benzodiazepin-2-ones and Their Affinity Toward CNS BenzodiazepineReceptors. -The products are used to study their affinity towards central nervous system and peripheral benzodiazepine receptors by in vitro radioligand method. -(PAVLOVSKY, V. I.; BACHINSKII, S. Y.; TKACHUK, N. A.; MAKAN, S. Y.; ANDRONATI, S. A.; SIMONOV, Y. A.; FILIPPOVA, I. G.; GDANIEC, M.; Chem.