Anticonvulsant Activity of the Linalool Enantiomers and Racemate: Investigation of Chiral Influence

• Published in: Natural product communications Vol. 5; no. 12; pp. 1847 - 1851
• Main Authors: de Sousa, Damião P., Nóbrega, Franklin F. F., Santos, Camila C. M. P., de Almeida, Reinaldo N.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.12.2010
• Subjects: Animals; Anticonvulsants - pharmacology; Male; Mice; Monoterpenes - chemistry; Monoterpenes - pharmacology; Stereoisomerism; Structure-Activity Relationship; epileptic seizure; anticonvulsant activity; essential oils; structure-activity relationship; terpenes
• ISSN: 1934-578X; 1555-9475
• DOI: 10.1177/1934578X1000501201

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.