Improvement of the anxiolytic-like effect of candesartan by its SOD mimetic copper(II) complex

CASARSA, BS; RODRIGUEZ, I; WILLIAMS, P.A.M.; BAIARDI, G.; BREGONZIO, C

Córdoba

Encuentro; Reunión Internacional de Ciencias Farmacéuticas Ricifa 2014; 2014

UNC

Improvement of the anxiolytic-like effect of candesartan by its SOD mimetic copper(II) complex Casarsa BS1, Rodriguez I2, Williams PAM3, Baiardi G1, Bregonzio C2 Lab. Neurofarmacología, FCQ, Universidad Católica de Córdoba, IIByT-CONICET1 Dep. Farmacología, FCQ, Universidad Nacional de Córdoba, IFEC-CONICET2 Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP)-Facultad de Ciencias Exactas, Universidad Nacional de La Plata.3   There is a large body of evidence, supporting a key role for Ang II in the stress response acting through its AT1 receptors. It has been already found that candesartan cilexetil (AT1 receptor blocker) administered orally has an anxiolytic effect when tested in the plus maze. Most of the sartans are composed of an appropriately substituted heterocyclic nucleus coupled to an acidic group (carboxylic or tetrazole) bearing biphenyl system through a methylene linker. Candesartan has the benzimidazole moiety substituted with carboxyl functional group at the7-position. Modifications of the structure of candesartan by the generation of pharmacodynamic hybrids with antioxidants or NO releasing drugs showed to improve the biological effect of the sartan. Based on previous evidence it was undertaken the design of another class of hybrids by synthesizing coordination compounds with the biometal copper(II) and candesartan. The aim of the present work was to compare the anxiolytic effects of candesartan cilexetil (Cand) and the new candesartan complex [Cu(Cand)(H2O2)4](Cu-Cand). For this purpose, Wistar male rats (250-320 g) were administered orally with Cand or Cu-Cand (3mg/kg), vehicle (NaHCO3  0.1N) or Cu (freshly prepared) during 5 days. On day 6 the animals were tested for 5 min in the plus maze to analyze the time spent in the open arms and extreme arrivals as anxiolytic measurements and total entries as locomotor activity index. The data were analyzed using two-way Anova. The results showed an increase in the anxiolytic parameters in the Cu-Cand respect Cand group. Cu was not significant from vehicle. Neither of the compounds affected the locomotor activity. Cu-Cand showed to be more effective as anxiolytic than Cand.