title: Effects of Insecticidal Ketones Present in Mint Plants on GABAAReceptor from Mammalian Neurons.
abstract: BACKGROUND
  The genusMentha, an important member of theLamiaceaefamily, is represented by many species commonly known as mint. The insecticidal activity ofMenthaoil and its main components has been tested and established against various insects/pests. Among these, the ketone monoterpenes that are most common in differentMenthaspecies demonstrated insect toxicity, with pulegone being the most active, followed by carvone and menthone. Considering that the GABAAreceptor (GABAA-R) is one of the main insecticide targets on neurons, and that pulegone would modulate the insect GABA system, it may be expected that the insecticidal properties ofMenthaketones are mediated by their interaction with this receptor.
  
  
  OBJECTIVE
  In order to discern the pharmacological actions of these products when used as insecticides on mammalian organisms, we evaluated the pharmacologic activity of ketones, commonly present inMenthaplants, on native GABAA-R from rats.
  
  
  METHODS
  Determination of ketones effects on allosterically enhanced benzodiazepine binding, using primary cultures of cortical neurons, which express functional receptors and MTT assay to evaluate their cell toxicity.
  
  
  RESULTS
  Our results seem to indicate that ketone components ofMentha, with proven repellent or insecticide activity, were able to behave as GABAA-R negative allosteric modulators in murine cells and consequently could exhibit convulsant activity in mammalians. Only pulegone at the highest assayed concentration (2 mM) showed a significant reduction in cell viability after exposure for 24 hr.
  
  
  CONCLUSIONS
  The present results strongly suggest that the ketone components ofMenthaare able to exhibit convulsant activity in mammalian organisms, but functional assays andin vivoexperiments would be necessary to corroborate this proposed action.
  
  
  CONCLUSIONS
  The pharmacological activity of insecticide ketones, commonly present inMenthaplants, was evaluated on native GABAAreceptor from mammalian neurons.All studied compounds: pulegone, menthone and dihydrocarvone, were able to behave as negative allosteric modulators and could exhibit convulsant activity in mammalian organisms.Citotoxicity assays demonstrated that only pulegone affected the cell viability.Abbreviations used:GABA: gamma aminobutyric acid, GABAA-R: GABAA receptor, MTT: 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazam, DMEM: Dulbecco's modified minimum essential mèdium, [3H]TBOB: [3H] t-Butylbicycloorthobenzoate.
authors.affiliation: Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT), CONICET-Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, Córdoba 5016, Argentina.
authors.forename: Mariela Eugenia
authors.initials: ME
authors.lastname: Sánchez-Borzone
authors.affiliation: Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT), CONICET-Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, Córdoba 5016, Argentina.
authors.forename: Leticia Delgado
authors.initials: LD
authors.lastname: Marin
authors.affiliation: Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT), CONICET-Universidad Nacional de Córdoba, Av. Vélez Sarsfield 1611, Córdoba 5016, Argentina.
authors.forename: Daniel Asmed
authors.initials: DA
authors.lastname: García
keywords: Cell culture; GABAA receptor; Mentha; insecticide; ketones; toxicity