Nitya Selvaraj1, Mangaiarkkarasi Adhimoolam2, Deepa Kameswari Perumal3, Meher Ali Rajamohammed4. 1. Assistant Professor, Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital , Puducherry, India . 2. Professor, Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital , Puducherry, India . 3. Post Graduate Student, Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital , Puducherry, India . 4. Professor and Head, Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital , Puducherry, India .
Abstract
BACKGROUND: The available conventional antiepileptics do not afford cure or prophylactic treatment and henceforth there is always a quest to explore new targets for management of convulsions. In this perspective, dihydropyridine calcium channel blockers have been investigated in various animal models of epilepsy. Lercanidipine, a newer dihydropyridine calcium antagonist, is a potential candidate with its favourable lipid profile and longer duration of action. OBJECTIVE: (1) To evaluate the anticonvulsant effect of lercanidipine alone and in combination with standard drug in adult male Swiss albino mice. (2) To evaluate the muscle relaxant and spontaneous locomotor activity of lercanidipine in adult male Swiss albino mice. MATERIALS AND METHODS: Adult male Swiss albino mice weighing 20-30g were used to study the anticonvulsant, muscle relaxant and spontaneous locomotor activity using electroconvulsometer, rotarod and actophotometer apparatus respectively. The mice were divided into six groups of six animals in each group. Group 1 and 2 served as control (vehicle treated) and standard group respectively. Standard drug used to evaluate anticonvulsant effect is phenytoin sodium 25 mg/kg I.P. whereas muscle relaxant activity and locomotor activity is diazepam 4 mg/kg I.P., Group 3 and 4 received lercanidipine 1 and 3 mg/kg I.P., respectively. Anticonvulsant models included group 5 and 6 and they were given combination of phenytoin sodium 12.5 mg/kg I.P., with lercanidipine 1 and 3 mg/kg i.p, respectively. Abolition or reduction of tonic hind limb extension was considered as index of anticonvulsant activity whereas the balancing time of the animals in rod was recorded to asses muscle relaxant activity. The locomotor activity was recorded for 5 minutes. The data were analysed with one-way Analysis of Variance followed by post-hoc 'Dunnett t-test'. RESULTS: Lercanidipine given alone in a dose of 1 and 3 mg/kg had significantly reduced the tonic hind limb extension. Combination of lercanidipine (3 mg/kg) and phenytoin had offered 100% protection. The results also revealed that the test drug didn't impair the motor coordination and locomotor activity in mice. CONCLUSION: The present study had demonstrated that lercanidipine could be potential novel candidate for the treatment of convulsions.
BACKGROUND: The available conventional antiepileptics do not afford cure or prophylactic treatment and henceforth there is always a quest to explore new targets for management of convulsions. In this perspective, dihydropyridine calcium channel blockers have been investigated in various animal models of epilepsy. Lercanidipine, a newer dihydropyridine calcium antagonist, is a potential candidate with its favourable lipid profile and longer duration of action. OBJECTIVE: (1) To evaluate the anticonvulsant effect of lercanidipine alone and in combination with standard drug in adult male Swiss albino mice. (2) To evaluate the muscle relaxant and spontaneous locomotor activity of lercanidipine in adult male Swiss albino mice. MATERIALS AND METHODS: Adult male Swiss albino mice weighing 20-30g were used to study the anticonvulsant, muscle relaxant and spontaneous locomotor activity using electroconvulsometer, rotarod and actophotometer apparatus respectively. The mice were divided into six groups of six animals in each group. Group 1 and 2 served as control (vehicle treated) and standard group respectively. Standard drug used to evaluate anticonvulsant effect is phenytoin sodium 25 mg/kg I.P. whereas muscle relaxant activity and locomotor activity is diazepam 4 mg/kg I.P., Group 3 and 4 received lercanidipine 1 and 3 mg/kg I.P., respectively. Anticonvulsant models included group 5 and 6 and they were given combination of phenytoin sodium 12.5 mg/kg I.P., with lercanidipine 1 and 3 mg/kg i.p, respectively. Abolition or reduction of tonic hind limb extension was considered as index of anticonvulsant activity whereas the balancing time of the animals in rod was recorded to asses muscle relaxant activity. The locomotor activity was recorded for 5 minutes. The data were analysed with one-way Analysis of Variance followed by post-hoc 'Dunnett t-test'. RESULTS:Lercanidipine given alone in a dose of 1 and 3 mg/kg had significantly reduced the tonic hind limb extension. Combination of lercanidipine (3 mg/kg) and phenytoin had offered 100% protection. The results also revealed that the test drug didn't impair the motor coordination and locomotor activity in mice. CONCLUSION: The present study had demonstrated that lercanidipine could be potential novel candidate for the treatment of convulsions.
Authors: Jarogniew J Luszczki; Michal K Trojnar; Marcin P Trojnar; Zaneta Kimber-Trojnar; Beata Szostakiewicz; Anna Zadrozniak; Kinga K Borowicz; Stanislaw J Czuczwar Journal: Can J Physiol Pharmacol Date: 2008-03 Impact factor: 2.273