G. Aragão, L. M. Carneiro, Antônio P.F. Juniora, P. Bandeira, T. L. Lemos, G. Viana
{"title":"Evidence for Excitatory and Inhibitory Amino Acids Participation in theNeuropharmacological Activity of Alpha- and Beta-Amyrin Acetate","authors":"G. Aragão, L. M. Carneiro, Antônio P.F. Juniora, P. Bandeira, T. L. Lemos, G. Viana","doi":"10.2174/1874143600903010009","DOIUrl":null,"url":null,"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 penty- lenetetrazole- 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 anx- iolytic 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%, re- spectively, while decreases in the levels of aspartate, GABA and glutamate of 72, 55 and 60%, respectively were ob- served. In conclusion, our results showed that AcAMY presents sedative, anxiolytic and anticonvulsant properties. Al- though 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.","PeriodicalId":22907,"journal":{"name":"The Open Pharmacology Journal","volume":"25 12","pages":"9-16"},"PeriodicalIF":0.0000,"publicationDate":"2009-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"18","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Open Pharmacology Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1874143600903010009","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 18
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 penty- lenetetrazole- 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 anx- iolytic 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%, re- spectively, while decreases in the levels of aspartate, GABA and glutamate of 72, 55 and 60%, respectively were ob- served. In conclusion, our results showed that AcAMY presents sedative, anxiolytic and anticonvulsant properties. Al- though 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.