title: Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action.
abstract: The aim of the study is to determine the acute toxicity and anxiolytic-like effects of a mixture of cis and trans of (+)-limonene epoxide in animal models of anxiety. After acute treatment with (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg (i.p.) no mortality was noted during 14 days of observation. In general, behavior, food and water consumption showed no significant changes. In open field test, (+)-limonene epoxide at doses of 25, 50 and 75 mg/kg, after intraperitoneal administration, significantly decreased the number of crossings, grooming and rearing (p<0.001). All these effects were reversed by the pre-treatment with flumazenil (25 mg/kg, i.p.), similar to those observed with diazepam used as a positive standard. In the elevated-plus-maze test, (+)-limonene epoxide increased the time of permanence and the number of entrances in the open arms. All these effects were reversed by flumazenil, an antagonist of benzodiazepine receptors. In addition, (+)-limonene epoxide (75 mg/kg) also produced a significant inhibition of the motor coordination (p<0.01), that was reversed by flumazenil. In conclusion, the present work evidenced sedative and anxiolytic-like effects of (+)-limonene epoxide, which might involve an action on benzodiazepine-type receptors. These results indicate that the properties of (+)-limonene epoxide should be more thoroughly examined in order to achieve newer tools for management and/or treatment of central nervous system diseases and anxiolytic-like effects. The LD50 obtained for the acute toxicity studies using intraperitoneal route of administration was 4.0 g/kg. These findings suggest that acute administration of the (+)-limonene epoxide exerts an anxiolytic-like effect on mice, and it could serve as a new approach for the treatment anxiety, since it practically does not produce toxic effects.
authors.affiliation: Department of Chemistry of Federal University of Piauí, CEP 64.049-550, Teresina, Piauí, Brazil.
authors.forename: Antonia Amanda C
authors.initials: AA
authors.lastname: de Almeida
authors.forename: Jéssica Pereira
authors.initials: JP
authors.lastname: Costa
authors.forename: Rusbene Bruno F
authors.initials: RB
authors.lastname: de Carvalho
authors.forename: Damião Pergentino
authors.initials: DP
authors.lastname: de Sousa
authors.forename: Rivelilson Mendes
authors.initials: RM
authors.lastname: de Freitas
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents; D001007:Anxiety / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D000081005:Cyclohexane Monoterpenes; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D006993:Hypnotics and Sedatives; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D014151:Anti-Anxiety Agents; D000081005:Cyclohexane Monoterpenes; D006993:Hypnotics and Sedatives; D039821:Monoterpenes; C028940:limonene-1,2-epoxide; D005442:Flumazenil; D003975:Diazepam