Influence of the chirality of (R)‐(−)‐ and (S)‐(+)‐carvone in the central nervous system: A comparative study

Abstract

Many terpenes are used therapeutically, and as flavor and fragrance materials. (R)-(-)-Carvone, the main constituent of spearmint oil, and (S)-(+)-carvone, found as major component of caraway and dill seed oils, have several applications and are used in cosmetic, food, and pharmaceutical preparations. In this study, the effect of enantiomers of carvone on the central nervous system (CNS) was evaluated in mice. The LD50 value was 484.2 mg/kg (358.9-653.2) for (S)-(+)-carvone, and 426.6 (389.0-478.6) mg/kg for (R)-(-)-carvone. Both enantiomers caused depressant effects, such as decrease in the response to the touch and ambulation, increase in sedation, palpebral ptosis, and antinociceptive effects. (S)-(+)- and (R)-(-)-carvone caused a significant decrease in ambulation. (R)-(-)-Carvone appeared to be more effective than its corresponding enantiomer at 0.5 and 2.0 h after administration. However, (S)-(+)-carvone was slightly more potent at 1 h. In potentiating pentobarbital sleeping time, (R)-(-)-carvone was more effective than (S)-(+)-carvone at 100 mg/kg, but was less potent at 200 mg/kg compared to the (+)-enantiomer, indicating a sedative action. (S)-(+)-Carvone at the dose of 200 mg/kg increased significantly the latency of convulsions induced by PTZ and PIC, but (R)-(-)-carvone was not effective against these convulsions. These results suggest that (S)-(+)-carvone and (R)-(-)-carvone have depressant effect in the CNS. (S)-(+)-Carvone appears to have anticonvulsant-like activity.

Anxiolytic-like effect of Lippia alba essential oil: A randomized, placebo-controlled trial

“…Besides, other studies found that L. alba essential oil (carvone chemotype) show anxiolytic effect in rats, pointing that carvone could be responsible for its action as a tranquilizer, due to its effect as a depressor of the central nervous system, interacting with GABA A receptors in the brain after crossing the blood-brain barrier [19]. Therefore, carvone attenuate neurons in limbic and septo-hippocampal systems, structures involved in suppressing the response of "active-avoidance" [34]. Other components related to exert an anxiolytic effect similar to that seen with diazepam are limonene and linalool [35], also present in the L. alba essential oil analyzed in this study.…”

Antinociceptive Activity of (-)-Carvone: Evidence of Association with Decreased Peripheral Nerve Excitability

“…1) found as the main active component of spearmint oil (Mentha spicata), a relative of common mint distilled from this plant. 8,9) Recently, our group has demonstrated that (Ϫ)-carvone derivatives, such as rotundifolone, 10) hydroxydihydrocarvone, 11) and epoxy-carvone 12) appear to have analgesic properties. Such compounds decreased the writhing nociceptive response induced by acetic acid in mice, 10,11) although the mechanisms underlying such properties remain unclear.…”

Antinociceptive Effect of Hydroxydihydrocarvone

“…These effects are probably due to the wide structural diversity of the components of essential oils 9) and, consequently, several of these components have been studied with the objective of identifying new bioactive molecules. Previous studies have shown that some monoterpenes present in many essential oils also induce antinociceptive, 10) anticonvulsant, 11,12) sedative, 13) and anxiolytic 14) effects in animals. Studies on monoterpene derivatives have also demonstrated various pharmacological properties, including antinociceptive 15,16) and antidepressant effects.…”