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The crude drug, Chotoko (Uncariae Uncis cam Ramlus), the hooks of Uncaria spp. (Rubiaceae), has been claimed to possess sedative and anti-spasmodic actions, and is contained in a Chinese traditional preparation, Choto-san, as a main crude drug. Examinations were made on the anti-convulsion effects of Choto-san and Chotoko against some animal models of epilepsy conducted by the stimulation of drugs or electricity. Oral administration of the Choto-san extract to mice at the doses of 1.0 g/kg and 3.0 g/kg tended to inhibit the glutamate-induced convulsion in a dose-dependent manner, and the effect of the Chotoko extract at a 3.0 g/kg dose was significant, while both the extracts showed no activity against the picrotoxine-induced, strychinine-induced, and electroshock convulsions. The Choto-san preparation without Chotoko was inactive, and the activity of the Chotoko extract was more potent than that of the every crude drug comprising Choto-san, suggesting that Chotoko plays the most important role in the Choto-san prescription and contains some active compounds. Bioassay-guided fractionation of the Chotoko extract led to the location of the active components in the less polar alkaloids-containing fraction, from which three indole alkaloids, geissoschizine methylether (1), hirsuteine (2) and hirsutine (3), and an oxyindole alkaloid, isocorynoxeine (4) were isolated and identified. Oral administration of 1 and 2 to mice at the doses of 50, 100, and 200 mg/kg inhibited the glutamate-induced convulsion in a dose-dependent manner. The effect of 3, the dihydro derivative of 2, was less potent than those of 1 and 2. Compound 4 showed no activity at a 100 mg/kg dose compared with control. The above results support the Chinese herbal description of the anti-spasmodic action of Chotoko, and show that 1 and 2 contained in Chotoko must be mainly contributed to the activity. It is also suggested that Choto-san may be clinically available for treatment of epilepsy.

Anti-convulsion Effects of Choto-san and Chotoko (Uncariae Uncis cam Ramlus) in Mice, and Identification of the Active Principles