Anticonvulsant activity of delta-HCH, calcium channel blockers and calmodulin antagonists in seizures induced by lindane and other convulsant drugs.
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)
Tusell
J M
JM
Department of Neurochemistry, CSIC, Barcelona, Spain.
Barrón
S
S
Serratosa
J
J
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003292:Convulsants / Q000037:antagonists & inhibitors; D001556:Hexachlorocyclohexane / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013237:Stereoisomerism; D013449:Sulfonamides / Q000494:pharmacology
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D002147:Calmodulin; D003292:Convulsants; D013449:Sulfonamides; D001556:Hexachlorocyclohexane; C017967:W 7; D009543:Nifedipine