title: Depressant effects of Agastache mexicana methanol extract and one of major metabolites tilianin.
abstract: OBJECTIVE
  To determine the depressant-like effects and the possible mechanism of action of tilianin isolated from active methanol extract of Agastache 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/kg po.) from A. 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/kg ip. 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/kg ip.) 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 of A. mexicana, reinforcing its central nervous system uses, where GABAA/BZD, but not 5-HT1A, receptors are partially involved.
authors.affiliation: Laboratorio de Neurofarmacología de Productos Naturales de la Dirección de Investigaciones en Neurociencias. Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", México, D.F.14370, México.
authors.forename: María Eva
authors.initials: ME
authors.lastname: González-Trujano
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
authors.forename: Hilda
authors.initials: H
authors.lastname: Ponce-Muñoz
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
authors.forename: Sergio
authors.initials: S
authors.lastname: Hidalgo-Figueroa
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México. Electronic address: enoch@uaem.mx.
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
keywords: Agastache mexicana; Anxiety; Benzodiazepine; Central nervous system; Sedative; Tilianin