Heteropterys brachiata is a plant species that has been used in traditional Mexican medicine for the treatment of nervous disorders. To evaluate the anxiolytic, anticonvulsant, antidepressant and sedative effects produced by the methanolic extract of Heteropterys brachiata (HbMeOH) in ICR mice. Additionally, we determine the acute toxicity profiles of the extract and the presence of its main constituents. The neuropharmacological effects of the extract were evaluated using a variety of models, such as the elevated plus maze (EPM), the forced swimming test (FST), the pentobarbital potentiation test (PTBt), pentylenetetrazole-induced seizures test (PTZt), and the open field test (OFT). HPLC was employed for obtention of phytochemical profile. HbMeOH produced a significant antidepressant effect in FST at 500 and 750 mg/kg doses, while doses from 500 to 1500 mg/kg exhibited a clear dose-dependent anxiolytic activity in EPM. A dose of 500 mg/kg showed a significant anticonvulsant activity in PTZt and an absence of sedation effects in PTBt. The main compounds of HbMeOH were chlorogenic acid and chlorogenic acid methyl ester, as well as less abundant terpene-type compounds. Furthermore, the extract was either safe with no deaths in mice treated orally with 2000 mg/kg. HbMeOH extract which contains mainly hydroxycinnamic acids and triterpene-type compounds, possesses antidepressant, anxiolytic and anticonvulsive properties and can be considered safe or of low toxicity when orally administrated. These findings lend pharmacological justification to the traditional use of Heteropterys brachiata in the treatment of nervous disorders. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.