Neuropharmacological effects of epinepetalactone from Nepeta sibthorpii behavioral and anticonvulsant activity

Several cyclopentanoid monoterpenes related to the iridoid compounds (nepetalactones) have been isolated and characterized in many Nepeta species. We studied the neuropharmacological activity of Nepeta sibthorpii Bentham essential oil (1.5 mg/kg i.p.), methanol extract (50 mg/kg i.p. and p.o.), and fraction containing epinepetalactone (Fraction 1) obtained from methanol extract (dose corresponding to 50 mg/kg of methanol extract i.p. and p.o.) in rodents. N. sibthorpii preparations produced definite alterations in general behavior pattern, potentiation of sodium pentobarbital-induced sleeping time, and protection against pentylenetetrazol (PTZ)-induced convulsions. The number of convulsions was significantly decreased after treatment with methanol extract (0.6 +/- 0.5), fraction 1 (0.6 +/- 0.9), and essential oil (0.7 +/- 0.9) in comparison with the group treated only with PTZ (3.0 +/- 0.5). The pretreatment of mice with flumazenil (3 mg/kg, i.p.), a benzodiazepine antagonist, blocked the anticonvulsant effect of all preparations. In our experimental conditions, methanol extract was the most active preparation. The depressant effect of Nepeta sibthorpii preparations on the CNS appears to involve GABA(ergic) mediation. This effect is certainly related to epinepetalactone, but in methanol extract other active principles are present.