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Anticonvulsant activity of delta-HCH, calcium channel blockers and calmodulin antagonists in seizures induced by lindane and other convulsant drugs.

Abstract
The anticonvulsant activity of delta-HCH and of a calmodulin antagonist, W-7 were investigated on convulsions induced in mice by lindane (ED100 100 mg/kg), by GABAergic antagonists PTZ (ED100 60 mg/kg) and PTX(ED100 4 mg/kg), by calcium channel agonist BAY-K-8644 (ED100 5 mg/kg), by two agonists of excitatory amino acid receptors, kainic acid (ED100 80 mg/kg) and NMDA (ED100 160 mg/kg and by the atypical benzodiazepine Ro 5-4864 (ED100 40 mg/kg). The anticonvulsant activity of a voltage-dependent calcium channel antagonist, nifedipine was also investigated on convulsions induced by Ro 5-4864, BAY-K-8644, kainic acid and NMDA. delta-HCH antagonized lindane- and BAY-K-8644-induced convulsions (ED50 231 (172-309) mg/kg and 148 (142-154) mg/kg, respectively) and at concentrations up to 300 mg/kg failed to antagonize Ro 5-4864, kainic acid and NMDA convulsions. In contrast delta-HCH potentiated PTX-induced seizures. Nifedipine antagonized BAY-K-8644- and kainic acid-induced convulsions (ED50 6.5 (4.3-9.7) mg/kg and 30 (13-70) mg/kg but at concentrations up to 20 mg/kg failed to antagonize Ro 5-4864 and 25% of protection was observed on NMDA-induced convulsions at the highest dose (20 mg/kg). The ED50 of W-7 to antagonize convulsions induced by lindane and BAY-K-8644 were 12 (8-19) mg/kg and 49 (29-85) mg/kg, respectively. Some anticonvulsant effect was observed against PTZ and NMDA but without any dose-dependent anticonvulsant activity. W-7 did not protect against PTX and kainic acid convulsions and 30% of protection was observed against convulsions at the highest dose of W-7 (75 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsJ M Tusell, S Barrón, J Serratosa
JournalBrain research (Brain Res) Vol. 622 Issue 1-2 Pg. 99-104 (Sep 17 1993) ISSN: 0006-8993 [Print] Netherlands
PMID7694769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticonvulsants
  • Calcium Channel Blockers
  • Calmodulin
  • Convulsants
  • Sulfonamides
  • Hexachlorocyclohexane
  • W 7
  • Nifedipine
Topics
  • Animals
  • Anticonvulsants (therapeutic use)
  • Calcium Channel Blockers (therapeutic use)
  • Calmodulin (antagonists & inhibitors)
  • Convulsants (antagonists & inhibitors)
  • Hexachlorocyclohexane (antagonists & inhibitors, therapeutic use)
  • Male
  • Mice
  • Nifedipine (pharmacology)
  • Seizures (chemically induced, drug therapy)
  • Stereoisomerism
  • Sulfonamides (pharmacology)

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