Anticonvulsant effect of lercanidipine against pentylenetetrazole induced kindling in mice


  • Nitya Selvaraj Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital, Kalitheerthal kuppam, Madagadipet, Puducherry 605107, India
  • Deepa Kameswari Department of Pharmacology, Aarupadai Veedu Medical College and Hospital, Cuddalore road, Kirumampakkam, Puducherry 607402, India
  • Ramya Gandhi Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital, Kalitheerthal kuppam, Madagadipet, Puducherry 605107, India
  • Meher Ali Raja Mohamad Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital, Kalitheerthal kuppam, Madagadipet, Puducherry 605107, India



Anticonvulsant, Kindling, Lercanidipine, Pentylenetetrazole


Background: Emerging evidence has demonstrated the role of high-voltage -sensitive activated dihydropyridine (L-type, CaV1.x) channels in the development of epilepsy. Based on that we hypothesized that lercanidipine, a dihydropyridine calcium channel blocker, would protect against Pentylenetetrazole (PTZ) induced kindling in mice model of epilepsy.

Methods: Kindling was induced in Swiss albino mice with PTZ in subconvulsive dose (30 mg/kg i.p.) thrice a week for nine weeks and the effect was scored using ‘4 point scoring system’. Rechallenging on the 3rd and 10th day with the same dose of PTZ was carried out after the last chronic dose.

Results: The data of the present study demonstrated that pretreatment with lercanidipine (½ h before PTZ, in doses of 1 and 3 mg/kg i.p. daily) alone and in combination with diazepam (2mg/kg i.p.) had decreased the incidence and severity of seizure as well as prolonged the onset of kindling in a dose-dependent manner (p <0.05). On rechallenging, lercanidipine resulted in reduction of seizure score (p <0.05) and increased the seizure latency.

Conclusions: The present study suggested that lercanidipine offered neuroprotection against PTZ induced kindling in mice.


Lowenstein DH. In: Harrison’s Principles of Internal Medicine. 18th Ed. New York: McGraw-Hill; Seizures and epilepsy. (eds): Braunwald E, Fauci AS, Hauser SL, Kasper DL, Longo DL, Jameson JL, Loscalzo J; 2012:3259-3270.

Cohen L. Epilepsy as a social problem. Br Med J. 1958;1(5072):672-5.

Bazil CW, Pedley TA. Advances in the medical treatment of epilepsy. Ann Rev Med. 1998;49:135-62.

Wong IC, Lhatoo SD. Adverse reactions to new anticonvulsant drugs. Drug Saf. 2000;23(1):35-56.

Pumain R, Kurcewicz I, Louvel J. Fast extracellular calcium transients: involvement in epileptic processes. Science. 1993;222(4620):177-9.

Kryzhanovskiĭ GN, Karpova MN, Abrosimov IIU, Pankov OIU, Lakinina MV. Anticonvulsant activity of sodium valproate and various calcium antagonists during their combined use in Mice. Biull Eksp Biol. Med 1993;115(3):231-3.

Rao SKN, Subbalakshmi NK. An experimental study of the anticonvulsant effect of amlodipine in mice. Singapore Med J. 2010;51(5):424-8.

Khanna N, Bhalla S, Verma V, Sharma KK. Modulatory effects of nifedipine and nimodipine in experimental convulsions. Indian J Pharmacol. 2000;32:347-52.

Luszczki JJ, Trojnar MK, Trojnar MP, Kimber-Trojnar Z, Szostakiewicz B, Zadrozniakn A, et al. Effects of amlodipine, diltiazem, and verapamil on the anticonvulsant action of topiramate against maximal electroshock-I induced seizures in mice. Can J Physiol Pharmacol. 2008;86(3):113-21.

Selvaraj N, Adhimoolam M, Perumal DK, Rajamohammed MA. Neuroprotective Effect of Lercanidipine- A Novel Calcium Channel Blocker in Albino Mice. J Clin Diagn Res. 2015;9(11):1-5.

Kupferbergh. Animal models used in the screening of antiepileptic drugs. Epilepsia. 2001;42(4):7-12.

Dhir A. Pentylenetetrazol (PTZ) Kindling Model of Epilepsy. Current Protocols in Neuroscience 2012;58:9.37.1-9.37.12.

Kulkarni SK. Handbook of Experimental Pharmacology. 3rd Ed. Mumbai: Vallabh Prakashan; Experiment on intact preparation: Pharmacology of CN; 1999:131-134.

Kulkarni SK, George B. Pentylenetetrazol-induced kindling in animals: protective effect of BR-16A. Indian J Exp Biol. 1995;33(6):424-7.

McNamara JO. Kindling model of epilepsy. Adv Neurol. 1986;44:303-18.

Simeone KA, Sabesan S, Kim DY, Kerrigan JF, Rho JM, Simeone TA. L-Type calcium channel blockade reduces network activity in human epileptic hypothalamic hamartoma tissue. Epilepsia. 2011;52(3):531-40.

Giorgi O, Orlandi M, Lecca D, Corda MG. MK-801 prevents chemical kindling induced by pentylenetetrazol in rats. Eur J Pharmacol. 1991;193(3):363-5.

Dibas MI, Dillon GH. The central nervous system convulsant pentylenetetrazole stimulates gamma-aminobutyric acid (GABA)-activated current in picrotoxin-resistant GABA(A) receptors in HEK293 cells. Neurosci Lett. 2000;285(3):193-6.

Borowicz KK, Czuczwar SJ. Effects of three calcium channel antagonists (amlodipine, diltiazem and verapamil) on the protective action of lamotrigine in the mouse maximal electroshock-induced seizure model. Pharmacological Reports. 2007;59(672):672-82.

Takahashi T, Momiyama A. Different types of calcium channels mediate central synaptic transmission. Nature. 1993;366(6451):156-8.

Brahmane RI, Wanmali VV, Pathak SS, Salwe KJ. Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice. J Pharmacol Pharmacother. 2010;1(2):78-81.

Bachmeier C, Beaulieu-Abdelahad D, Mullan M, Paris D. Selective dihydropyiridine compounds facilitate the clearance of β-amyloid across the blood-brain barrier. Eur J Pharmacol. 2011;659(2-3):124-9.




How to Cite

Selvaraj, N., Kameswari, D., Gandhi, R., & Raja Mohamad, M. A. (2017). Anticonvulsant effect of lercanidipine against pentylenetetrazole induced kindling in mice. International Journal of Basic & Clinical Pharmacology, 6(9), 2134–2139.



Original Research Articles