Evaluation of anxiolytic, sedative-hypnotic and amnesic effects of novel 2-phenoxy phenyl-1,3,4-oxadizole derivatives using experimental models

Benzodiazepines [BZDs] are widely used in clinical practice as anxiolytics, hypnotics, anticonvulsants and muscle relaxants. However, they have some undesired effects including memory problems. In continuing our research on novel benzodiazepine ligands, we are looking for ligands with less adverse effects. Previously, 4 novel derivatives of 2-phenoxy phenyl-1,3,4-oxadiazole were synthesized as agonists of BZD receptors. In this study, the pharmacological effects of novel compounds were evaluated. Pentobarbital induced loss of righting reflex, elevated plus maze, open-field locomotor activity and passive avoidance test were used to evaluate the sedative-hypnotic, anxiolytic and amnesic effects of compounds respectively. The results revealed that the novel compounds with NH[2], SH and SCH[3] substituents at the 2-position of the oxadiazole ring increase righting reflex time significantly. In the elevated plus maze test none of the derivatives increased open arm duration and open arm entry indicating no anxiolytic properties. Moreover, the novel compounds didn't influence step-down latencies in the mice. The fact that the hypnotic activity of these compounds were significantly reduced by flumazenil, confirmed that this effect is mediated by BZD receptors

BCL-2 and bax expression in skin flaps treated with finasteride or azelaic acid

Despite all modern surgical techniques, skin flap that is considered as the main method in most reconstructive surgeries puts the skin tissue at danger of necrosis and apoptosis derived from ischemia. Therefore, finding a treatment for decreasing the apoptosis derived from flap ischemia will be useful in clinic. In present study, we evaluated the effect of azelaic acid 20% and finasteride on expression of BCL-2 and bax proteins after the skin flap surgery. For this purpose, 21 rats were entered in three groups including control, azelaic acid 20% and finasteride, all experienced skin flap surgery and then flap tissue was assessed for determining the expression of proteins in 5 slices prepared from each rat that were graded between - to +++ scales. Both azelaic acid and finasteride increased the expression of BCL-2 protein [p < 0.05] and decrease the expression of bax protein [p < 0.05]. These results suggested an antiapoptotic role for finasteride and azelaic acid in preserving the flap after the ischemia reperfusion insult