ABSTRACT
Objective:To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract ofAgastache mexicana(A. mexicana).Also, to establish the pharmacophoric requirements of tilianin, as a possible ligand of GABAA/BZD receptor, by the alignment of diazepam, CGS-9896 and diindole, using a previously described pharmacophoric model.Methods:Tilianin (30 to 300 mg/kg,ip.and 300 mg/kg, po.)and methanol crude extract (10 to 300 mg/kg,ip. and 300 mg/kgpo.)fromA. mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field, hole-board, cylinder of exploration, plus-maze and sodium pentobarbital-induced hypnosis mice methods.Results:Methanol extract and tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg,ip.or 300 mg/kg,po.and were less potent than diazepam 0.1 mg/kg, a reference anxiolytic drug used. Moreover, depressant activity of both potentiates sodium pentobarbital (SP)-induced sleeping time. The anxiolytic-like effect of 30 mg/kgip.observed for the extract and tilianin, by using the plus-maze model, was partially prevented in the presence of flumazenil (a GABAA/BZD antagonist, 5 mg/kgip.)but not in the presence of WAY 100635 (a selective 5-HT1A receptor antagonist, 0.32 mg/kg,ip.).Pharmacophoric modeling alignments of three agonist of GABAA/BZD allow identify seven chemical features. Tilianin contains six of the seven features previously determined.Conclusions:Results indicate that tilianin is one of the bioactive metabolites in the anxiolytic-like activity ofA. mexicana, reinforcing its central nervous system uses, where GABAA/BZD, but not 5-HT1A, receptors are partially involved.