Evidence for Excitatory and Inhibitory Amino Acids Participation in the Neuropharmacological Activity of Alpha- and Beta-Amyrin Acetate

We evaluated the neuropharmacological profile of acetylated alphaand beta-amyrin (AcAMY) obtained by the acetylation of the isomeric mixture of alphaand beta-amyrin isolated from Protium heptaphyllum. Male Swiss mice were administered with AcAMY (2.5, 5, 10 and 25 mg/kg, i.p.), and anticonvulsant (pentylenetrazoleand pilocarpine-induced convulsions), sedative (barbiturate-induced sleep and open field tests) and anxiolytic (elevated plus maze test) activities were studied. Results showed that AcAMY administered intraperitoneally or orally, protected the animals against pentylenetetrazolebut not against pilocarpine-induced convulsions. The drug increased both the latency to the 1 st convulsion and the latency to death. The barbiturate-induced sleeping time was also increased, as well as the ethyl ether-induced sleeping time, confirming the sedative nature of AcAMY. The acute administration of AcAMY also produced an anxiolytic effect. After the sub-chronic administration, both sedative and anxiolytic effects were manifested, at the two higher doses. Amino acids measurements in brain areas of mice treated with AcAMY (25 mg/kg, i.p., for 7 days) showed an 89% increase in tyrosine levels, in the hippocampus. In the striatum, tyrosine and taurine were increased by 97 and 79%, respectively, while decreases in the levels of aspartate, GABA and glutamate of 72, 55 and 60%, respectively were observed. In conclusion, our results showed that AcAMY presents sedative, anxiolytic and anticonvulsant properties. Although the drug mechanism of action is not completely clarified, it seems to involve a decrease in excitatory amino acids and an increase of inhibitory amino acids. Furthermore, the GABAergic system may also play a role.