title: Anticonvulsant activity of the linalool enantiomers and racemate: investigation of chiral influence.
abstract: The anticonvulsant activity of the racemate and enantiomers of linalool have been evaluated. Pretreatment of the mice with (S)-(+)-, (R)-(-)- and rac-linalool increased the latency of convulsions significantly in the PTZ model. Only rac-linalool had an effect at the dose of 200 mg/kg. The enantiomers and their racemic mixture were effective in inhibiting the convulsant effect of PTZ at the dose of 300 mg/kg. The linalools presented pharmacological activity close to that of diazepam. In the PIC seizure model, (R)-(-)-linalool and rac-linalool presented activity at the dose of 200 mg/kg, but the rac-linalool was more potent than (R)-(-)-linalool; (S)-(+)-linalool had no effect at this dose. On the other hand, at the dose of 300 mg/kg this enantiomer was effective, but less potent than (R)-(-)-linalool and rac-linalool. In the MES model, linalools decreased the convulsion time of the mice in the doses of 200 and 300 mg/kg. rac-Linalool presented maximum effect at 300 mg/kg. Surprisingly, it increased significantly the convulsion time at a dose of 100 mg/kg. Using the parameter of tonic hind convulsions, only (R)-(-)-linalool produced protection from tonic extension at the dose of 200 mg/kg. When the (+)- and (-)-enantiomers, and rac-linalool were administered at the dose of 300 mg/kg they were also effective in preventing tonic convulsions induced by transcorneal electroshock in the animals. The (+)- and (-)-forms were equipotent and the rac-linalool was more effective than phenytoin. We have demonstrated that the two enantiomers have similar qualitative anticonvulsant activity, but show different potencies.
authors.affiliation: Departamento de Fisiologia/Universidade Federal de Sergipe, Aracaju, Sergipe, Brazil, CEP 49100-000. damiao_desousa@yahoo.com.br
authors.forename: Damião P
authors.initials: DP
authors.lastname: de Sousa
authors.forename: Franklin F F
authors.initials: FF
authors.lastname: Nóbrega
authors.forename: Camila C M P
authors.initials: CC
authors.lastname: Santos
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: de Almeida
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000080462:Acyclic Monoterpenes; D000927:Anticonvulsants; D039821:Monoterpenes; C018584:linalool