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)