Isobolographic analysis of the sedative interaction between six central nervous system depressant drugs and Valeriana edulis hydroalcoholic extract in mice*

Abstract

It has been declared frequently that valerian may potentiate the effect of other central nervous system (CNS) depressant drugs, however there has been a lack of experimental data. We have evaluated the profile of the interactions between the ethanol extract of Valeriana edulis spp procera and six CNS depressant drugs using an exploratory model to test the sedative effect in mice. All the compounds tested showed a dose-dependent sedative effect with the following ED50 values: valerian 181.62, diazepam 1.21, ethanol 1938, pentobarbital 11.86, buspirone 1.04, haloperidol 0.41 and diphenhydramine 17.06 mg kg−1. An isobolographic analysis was used to evaluate the sedative interaction of the intraperitoneal co-administration of 1:1 fixed-ratio combination of equi-effective doses of valerian extract with each CNS depressant drug. The ED50 theoretical (Zadd) and experimental (Zexp) for each combination were: valerian + diazepam, Zadd = 91.41 mg kg−1, Zexp = 81.64 mg kg−1; valerian + ethanol, Zadd = 1060.22 mg kg−1, Zexp = 687.89 mg kg−1; valerian + pentobarbital, Zadd = 96.74 mg kg−1, Zexp = 151.83 mg kg−1; valerian + buspirone, Zadd = 91.33 mg kg−1, Zexp = 112.73 mg kg−1; valerian + haloperidol, Zadd = 91.01 mg kg−1, Zexp = 91.52 mg kg−1; valerian + diphenhydramine, Zadd = 99.34 mg kg−1, Zexp = 123.52 mg kg−1. Neither synergistic nor attenuate effects were found in any of the combinations evaluated. We concluded that the valerian extract did not potentiate the sedative effect of commonly prescribed CNS depressant drugs as was expected. The additive effect found through the isobolographic analysis suggested that the sedative effect of V. edulis resulted from the activation of common mechanisms of haloperidol, diazepam, buspirone, pentobarbital, diphenhydramine and ethanol.