Isobolographic analysis of the sedative interaction between six central nervous system depressant drugs andValeriana edulishydroalcoholic 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.

Synthesis and Nootropic Activity of Some 2,3‐Dihydro‐1H‐isoindol‐1‐one Derivatives Structurally Related with Piracetam

“…The inner side of the apparatus and floor were cleaned with alcoholic soln. (10% v/v in H 2 O), and filter paper was changed between each animal test session [23] [24]. The drugs were administered 30 min before testing in different doses.…”

Anti-Nociceptive Synergism of Pregabalin and Xylopic acid Co-administration in Paclitaxel induced Neuropathy: Isobolographic Analysis

“…The additivity line represents the level of effect for the individual agents and the closeness of the experimental potency of the mixture to this line in the thermal pain test demonstrates additivity. 20 Both compounds were more potent in the thermal pain test compared to the cold allodynia test. On the contrary, the magnitude of potentiation, with reference to the interaction indices was greater in the cold allodynia test than the thermal pain test.…”

Toxic rather than neuropharmacological effect ofTernstroemia sylvaticafruits and identification of 28-O-[β-l-6-rhamnopyranosyl]-R1-barrigenol as a new compound with toxic effects in mice

“…The observations were made without prior knowledge of the experimental conditions applied to the animal. Reduced exploratory rearing showed by naïve mice after placement in an unfamiliar environment reveals a sedative effect (Hiller & Zetler, 1996;Oliva et al, 2004;Rolland et al, 1991;Ugalde et al, 2005).…”