“Tolerance to sedative effects. An alternative choice, hesperidin or diazepam?”

LOSCALZO, LEONARDO M.; WASOWSKI, CRISTINA; FERNÁNDEZ, SEBASTIÁN P.; PALADINI, ALEJANDRO C.; MARDER, MARIEL

Pinamar, Argentina

Congreso; X PABMB Congress-Panamerican Association for Biochemistry and Molecular Biology, SAIB, XLI Annual Meeting Sociedad Argentina de Investigación en Bioquímica y Biología Molecular y SAN, XX Annual Meeting Sociedad Argentina de Neuroquímica; 2005

PABMB, SAIB y SAN

Chronic treatment with benzodiazepines results in tolerance to their effects and the evidence points to different operating mechanisms. We have demonstrated that acute treatment with hesperidin (HN) or diazepam (DZ) has a dose-dependent response in the holeboard test. These compounds have similar efficacy and the co-administration of both drugs evidences a synergistic interaction in vivo. In the present work we compared the behavioral effects of chronic treatment with DZ, HN and HN-DZ fixed-ratio combinations. Mice were given daily i.p. injections of the drugs, and were assayed in the locomotor activity and holeboard tests after 7 days of treatment. Results indicate that HN does not produce the tolerance effects clearly manifested by DZ. Otherwise, the synergistic effects of HN-DZ fixed-ratio combinations were also present in the chronic treatment. It suggests that flavonoids, besides being potentially valuable single drugs, may also be used with advantage in combination with benzodiazepines.