Topiramate (TPM), a new generation antiepileptic drug was investigated for its anticonvulsant effects in various models of genetically determined and chemically induced epilepsy in rodents. In addition, based on recent electrophysiological data suggesting that TPM may interact with L-type Ca2+ channels, we evaluated the effects of a concomitant administration of L-type Ca2+ channel modulators on TPM's antiepileptic properties. TPM, dose-dependently, protected against audiogenic seizures in DBA/2 mice. Concomitant treatment with TPM and a low dose of L-type Ca2+ channel antagonists nifedipine or verapamil or with the L-type Ca2+ channel agonist. S(-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(triflouromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester (Bay k 8644) was able to increase the ED50 for this drug. TPM also protected against seizures induced by alpha-amino-3-hydroxy-5-methylisoxizole-4-propionic acid (AMPA), 4-aminopyridine (4-AP) and pentylenetetrazole (PTZ), but this activity was not significantly modified by nifedipine. TPM, dose-dependently, reduced the number and duration of epileptic spike-wave discharges (SWDs) both in WAG/Rij rats and lethargic (lh/lh) mice, two genetic models of absence epilepsy. Nifedipine decreased TPM's activity in WAG/Rij rats but paradoxically enhanced it in lh/lh mice, whereas Bay k 8644 displayed opposite effects in both absence models. These results confirm TPM's broad spectrum of anticonvulsant activity and support the proposal that a modulation of neuronal L-type Ca2+ channel activity plays an important role in its antiepileptic activity. (C) 2004 Elsevier Ltd. All rights reserved.
Topiramate (TPM), a new generation antiepileptic drug was investigated for its anticonvulsant effects in various models of genetically determined and chemically induced epilepsy in rodents. In addition, based on recent electrophysiological data suggesting that TPM may interact with L-type Ca2+ channels, we evaluated the effects of a concomitant administration of L-type Ca2+ channel modulators on TPM's antiepileptic properties. TPM, dose-dependently, protected against audiogenic seizures in DBA/2 mice. Concomitant treatment with TPM and a low dose of L-type Ca2+ channel antagonists nifedipine or verapamil or with the L-type Ca2+ channel agonist. S(-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(triflouromethyl)phenyl]-3-py ridinecarboxylic acid methyl ester (Bay k 8644) was able to increase the ED50 for this drug. TPM also protected against seizures induced by alpha-amino-3-hydroxy-5-methylisoxizole-4-propionic acid (AMPA), 4-aminopyridine (4-AP) and pentylenetetrazole (PTZ), but this activity was not significantly modified by nifedipine. TPM, dose-dependently, reduced the number and duration of epileptic spike-wave discharges (SWDs) both in WAG/Rij rats and lethargic (lh/lh) mice, two genetic models of absence epilepsy. Nifedipine decreased TPM's activity in WAG/Rij rats but paradoxically enhanced it in lh/lh mice, whereas Bay k 8644 displayed opposite effects in both absence models. These results confirm TPM's broad spectrum of anticonvulsant activity and support the proposal that a modulation of neuronal L-type Ca2+ channel activity plays an important role in its antiepileptic activity. (C) 2004 Elsevier Ltd. All rights reserved.
Nifedipine affects the anticonvulsant activity of topiramate in various animal models of epilepsy
RUSSO E;CITRARO R;DE SARRO G
2004-01-01
Abstract
Topiramate (TPM), a new generation antiepileptic drug was investigated for its anticonvulsant effects in various models of genetically determined and chemically induced epilepsy in rodents. In addition, based on recent electrophysiological data suggesting that TPM may interact with L-type Ca2+ channels, we evaluated the effects of a concomitant administration of L-type Ca2+ channel modulators on TPM's antiepileptic properties. TPM, dose-dependently, protected against audiogenic seizures in DBA/2 mice. Concomitant treatment with TPM and a low dose of L-type Ca2+ channel antagonists nifedipine or verapamil or with the L-type Ca2+ channel agonist. S(-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(triflouromethyl)phenyl]-3-py ridinecarboxylic acid methyl ester (Bay k 8644) was able to increase the ED50 for this drug. TPM also protected against seizures induced by alpha-amino-3-hydroxy-5-methylisoxizole-4-propionic acid (AMPA), 4-aminopyridine (4-AP) and pentylenetetrazole (PTZ), but this activity was not significantly modified by nifedipine. TPM, dose-dependently, reduced the number and duration of epileptic spike-wave discharges (SWDs) both in WAG/Rij rats and lethargic (lh/lh) mice, two genetic models of absence epilepsy. Nifedipine decreased TPM's activity in WAG/Rij rats but paradoxically enhanced it in lh/lh mice, whereas Bay k 8644 displayed opposite effects in both absence models. These results confirm TPM's broad spectrum of anticonvulsant activity and support the proposal that a modulation of neuronal L-type Ca2+ channel activity plays an important role in its antiepileptic activity. (C) 2004 Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
