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: Damião P de Sousa, Franklin F F Nóbrega, Camila C M P Santos, Reinaldo N de Almeida
• Journal: Natural product communications (Nat Prod Commun) Vol. 5 Issue 12 Pg. 1847-51 (Dec 2010) ISSN: 1934-578X [Print] United States
• PMID: 21299105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acyclic Monoterpenes
• Anticonvulsants
• Monoterpenes
• linalool

Topics

• Acyclic Monoterpenes
• Animals
• Anticonvulsants (pharmacology)
• Male
• Mice
• Monoterpenes (chemistry, pharmacology)
• Stereoisomerism
• Structure-Activity Relationship