ANTI-CONVULSION EFFECTS OF CHOTO-SAN, AND CHOTOKO (UNCARIAE UNCIS CAMRAMLUS) IN MICE, AND IDENTIFICATION OF THE ACTIVE PRINCIPLES

The crude drug, Chotoko (Uncariae Uncis cam Ramlus), the hooks of Unca ria spp. (Rubiaceae), has been claimed to possess sedative and anti-sp asmodic 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. Ora l 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 i n 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 activ ity against the picrotoxine-induced, strychinine-induced, and electros hock convulsions. The Choto-san preparation without Chotoko was inacti ve, 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 contai ns some active compounds. Bioassay-guided fractionation of the Chotoko extract led to the location of the active components in the less pola r alkaloids-containing fraction, from which three indole alkaloids, ge issoschizine methylether (1), hirusteine (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 20 0 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 d ose compared with control. The above results support the Chinese herba l 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.