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

ABSTRACT

We evaluated the neuropharmacological profile of acetylated alpha- and beta-amyrin (AcAMY) obtained by the acetylation of the isomeric mixture of alpha- and 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 (pentylenetrazole- and 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 pentylenetetrazole- but 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.

Keywords:

Burseraceae, Protium heptaphyllum, acetate of alpha- and beta-amyrin, sedative, anticonvulsant and anxiolytic effects.