Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers

Abstract

Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (´)-cis-EC, (+)-trans-EC, and (´)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg) increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES) test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+) and (´)-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+) and (´)-trans-EC (at 300 mg/kg) showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+)-cis-EC and (+)-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+)-cis-EC, (+)-trans-EC, and (´)-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes.

Comparison of behavioral, neuroprotective, and proinflammatory cytokine modulating effects exercised by (+)‐cis‐EC and (−)‐cis‐EC stereoisomers in a PTZ‐induced kindling test in mice

“…The stereoisomers (+)‐cis‐EC and (−)‐cis‐EC were synthesized and identified as described in the literature .…”

“…Test substances (stereoisomers of epoxy-carvone) The stereoisomers (+)-cis-EC and (À)-cis-EC were synthesized and identified as described in the literature [19][20][21].…”

“…The stereoisomers (+)‐cis‐epoxy‐carvone and (−)‐cis‐epoxy‐carvone are monoterpenes of natural origin . Obtainable by organic synthesis , their preliminary comparative anticonvulsant activity was characterized recently by behavioral methodologies, especially (+)‐cis‐epoxy‐carvone . Given the anticonvulsant potential of these stereoisomers, and the possibility of observing differences in their pharmacological effectiveness, the promise of studies on the influence of (+)‐cis‐epoxy‐carvone and (−)‐cis‐epoxy‐carvone on the hippocampi of animals by pentylenetetrazol‐induced kindling testing, this study aims to comparatively investigate the effect of stereoisomers (+)‐cis‐epoxy‐carvone and (−)‐cis‐epoxy‐carvone on behavioral changes, in the levels of cytokines IL‐1β, IL‐6, and TNFα and neuronal protection in the face of continuous treatment with pentylenetetrazol.…”

Anticonvulsant Essential Oils and Their Relationship with Oxidative Stress in Epilepsy

“…No significant results were obtained in the strychnine-induced seizure test for any of the isomers tested. In the model of maximal atrial electroshock, although they all significantly reduced seizure duration, there were differences in effect [196]. In the PTZ-induced kindling model with (+)-cis-EC and (-)-cis-EC, both reduce seizure severity and levels of proinflammatory cytokines IL-6 and TNF-α in mice hippocampi.…”

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“…Krishna Jiraka (C. carvi) [45][46][47][48][49][50] Aqueous extract and essential oil found to have anticonvulsant potential against scPTZ model. Epoxycarvone, a constituent of essential oil, also found to possess anticonvulsant potential against scPTZ and MES models.…”