The Chinese Herbal Medicine Chai-Hu-Long-Ku-Mu-Li-Tan (TW-001) Exerts Anticonvulsant Effects Against Different Experimental Models of Seizure in Rats

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Author(s)

Abstract

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 thresold 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(1-10mg/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(0.5-1.5mg/ml)in a concentration-dependent manner.The sensitivity of postsynaptic neurons to a glutamate-receptor agonist, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or N-methyl-D-aspartate, was not altered by TW-001(10mg/ml).However, TW-001(5mg/ml)clearly increased the magnitude of paired-pulse facilitation.TW-001(5-10mg/ml)reversibly limited the repetitive firing and reduced the maximal rate of rise of action potentials elicited by injection of depolarizing current pulses(0.4nA, 200ms)into the pyramidal cells.TW-001(1-10mg/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 channesl, stabilizing neuronal membrane excitability and inhibiting glutamate release.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 82(3), 247-260, 2000-03-01

    The Japanese Pharmacological Society

References:  36

Codes

  • NII Article ID (NAID)
    10008183600
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    5321090
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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