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 increased the threshold for tonic electroconvulsions and the threshold for tonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ). In the s.c. PTZ seizure test, both the incidence and severity of seizures were decreased by TW-001. TW-001 (1-10 mg/ml) did not alter resting membrane potential or input resistance of the hippocampal CA1 neurons, but elicited a reversible suppression of stimulus-triggered epileptiform activity in area CA1 and spontaneously occuring epileptiform burst discharges in area CA3 elicited by picrotoxin. Both field excitatory postsynaptic potentials and population spikes were reversibly depressed by TW-001 (0.5-15 mg/ml) in a concentration-dependent manner. The sensitivity of postsynaptic neurons to a glutamate-receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid 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 facilitation. TW-001 (5-10 mg/ml) reversibly limited the repetitive firing and reduced 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 tetrodotoxin-sensitive sodium currents and high voltage-activated calcium currents. These results suggest that TW-001 is an interesting new anticonvulsant agent that exerts its anticonvulsant activity through inhibition of sodium and calcium channels, stabilizing neuronal membrane excitability and inhibiting glutamate release.
Wu
H M
HM
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan.
Huang
C C
CC
Li
L H
LH
Tsai
J J
JJ
Hsu
K S
KS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy*; D015222:Sodium Channels / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000927:Anticonvulsants; D015220:Calcium Channels; D004365:Drugs, Chinese Herbal; D015222:Sodium Channels; C415127:TW 001