Anticonvulsant effect of a natural compound alpha,beta-epoxy-carvone and its action on the nerve excitability.

Abstract

The anticonvulsant effect of alpha,beta-epoxy-carvone (EC), a monoterpene monocyclic, was investigated in three animal models. EC at 300 or 400 mg/kg promoted protection of 75% and 87.5%, respectively, against convulsions induced chemically by pentylenetetrazole (PTZ) and it was efficient in prevents the tonic convulsions induced by maximal electroshock (MES) in doses of 200, 300 or 400 mg/kg, resulting in 25%, 25% and 100% of protection, respectively. This monoterpene was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at 300 or 400 mg/kg and presented a significant protection against convulsions at doses of 200, 300 or 400 mg/kg, resulting in 12.5%, 12.5% and 100% of protection, respectively. On the other hand, the anticonvulsant effect of EC, was not affected by pretreatment with flumazenil (FLU), a selective antagonist of benzodiazepine site of GABA(A) receptor. Additionally was observed that EC treatment reduced the levels of in vitro lipoperoxidation and decreased (21.2%) the amplitude of compound action potential after 30 min of incubation. The present results clearly indicate the ability of EC to modulate the anticonvulsant and antioxidant effects. However, our data suggests that the action mechanisms are not due a direct activation of the GABA(A) benzodiazepine receptors, but could be associated with the reduction of isolated nerve excitability, possibly involving a voltage-gated Na(+) channels blockade.

• Authors: Reinaldo Nóbrega de Almeida, Damião Pergentino de Sousa, Franklin Ferreira de Farias Nóbrega, Fladmir de Sousa Claudino, Demétrius Antonio Machado Araújo, José Roberto Leite, Rita Mattei
• Journal: Neuroscience letters (Neurosci Lett) Vol. 443 Issue 1 Pg. 51-5 (Sep 26 2008) ISSN: 0304-3940 [Print] Ireland
• PMID: 18657594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Convulsants
• Cyclohexane Monoterpenes
• GABA Modulators
• Monoterpenes
• Picrotoxin
• Flumazenil
• carvone
• Pentylenetetrazole

Topics

• Action Potentials (drug effects, physiology)
• Animals
• Anticonvulsants (therapeutic use)
• Convulsants (toxicity)
• Cyclohexane Monoterpenes
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Electroshock (adverse effects)
• Epilepsy (drug therapy, etiology, pathology)
• Flumazenil (therapeutic use)
• GABA Modulators (therapeutic use)
• In Vitro Techniques
• Male
• Mice
• Monoterpenes (therapeutic use)
• Pentylenetetrazole (toxicity)
• Physical Stimulation (methods)
• Picrotoxin (toxicity)
• Rats
• Rats, Wistar
• Sciatic Nerve (drug effects, physiopathology)