Evaluation of Anxiolytic, Sedative-Hypnotic and Amnesic Effects of Novel 2-Phenoxy Phenyl-1,3,4-Oxadizole Derivatives Using Experimental Models



Tabatabai SA¹ ; Rezaee E¹ ; Reyhanfard H¹ ; Alinezhad B² ; Shafaghi B² ; Sheikhha M³ ; Shafiee A³ ; Faizi M³ Show Affiliations
Source: Iranian Journal of Pharmaceutical Research Published:2015

Abstract

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 NH2, SH and SCH3substituents 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. © 2015 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services.