The Chinese herbal medicine Chai-Hu-Long-Ku-Mu-Li-Tan (TW-001) exerts anticonvulsant effects against different experimental models of seizure in rats

We evaluated the anticonvulsant effect of Chai-Hu-Long-Ku-Mu-Li-Tan (TW-001 ), a Chinese herbal medicine, and its mechanisms in several standard rodent models of generalized seizure. TW-001 (4 g/kg, p.o.) significantly increas ed the threshold for tonic electroconvulsions and the threshold for tonic s eizures in response to i.v. infusion of pentylenetetrazole (PTZ). In the s. c. PTZ seizure test, both the incidence and severity of seizures were decre ased by TW-001. TW-001 (1-10 mg/ml) did not alter resting membrane potentia l or input resistance of the hippocampal CA1 neurons, but elicited a revers ible suppression of stimulus-triggered epileptiform activity in area CA1 an d spontaneously occuring epileptiform burst discharges in area CA3 elicited by picrotoxin. Both field excitatory postsynaptic potentials and populatio n spikes were reversibly depressed by TW-001 (0.5 - 15 mg/ml) in a concentr ation-dependent manner. The sensitivity of postsynaptic neurons to a glutam ate-receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic a cid or N-methyl-D-aspartate, was not altered by TW-001 (10 mg/ml). However, TW-001 (5 mg/ml) clearly increased the magnitude of paired-pulse facilitat ion. TW-001 (5 - 10 mg/ml) reversibly limited the repetitive firing and red uced the maximal rate of rise of action potentials elicited by injection of depolarizing current pulses (0.4 nA, 200 ms) into the pyramidal cells. TW- 001 (1-10 mg/ml) exerted a concentration-dependent reduction of the tetrodo toxin-sensitive sodium currents and high voltage-activated calcium currents . These results suggest that TW-001 is an interesting new anticonvulsant ag ent that exerts its anticonvulsant activity through inhibition of sodium an d calcium channels, stabilizing neuronal membrane excitability and inhibiti ng glutamate release.