Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or clonazepam in amygdala-kindled rats.
Loreclezole (5 mg/kg) exerted a significant protective action in amygdala-kindled rats, reducing both seizure and afterdischarge durations. The combinations of loreclezole (2.5 mg/kg) with valproate, clonazepam, or carbamazepine (applied at their subprotective doses) also exhibited antiseizure effect in this test. However, only two first combinations occurred to be of pharmacodynamic nature. Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k-8644 (the opener of L-type calcium channels) reversed the protective activity of loreclezole alone and its combination with valproate. On the other hand, bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of loreclezole combined with clonazepam. The results support the hypothesis that the protective activity of loreclezole and its combinations with other antiepileptics may involve potentiation of GABAergic neurotransmission and blockade of L-type of calcium channels.
Borowicz
Kinga K
KK
Department of Pathophysiology, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland. kornel@asklepios.am.lublin.pl
Czuczwar
Stanisław J
SJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000628:Aminophylline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002220:Carbamazepine / Q000494:pharmacology; D002998:Clonazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003292:Convulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004338:Drug Combinations; D004347:Drug Interactions; D004567:Electrodes, Implanted; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D013238:Stereotaxic Techniques; D013331:Strychnine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D014635:Valproic Acid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics
D003292:Convulsants; D004338:Drug Combinations; D014230:Triazoles; D000628:Aminophylline; D002220:Carbamazepine; D002998:Clonazepam; D014635:Valproic Acid; D016202:N-Methylaspartate; C066440:loreclezole; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013331:Strychnine; D007608:Kainic Acid; D001640:Bicuculline