Evaluation of the anticonvulsant effect of nimodipine and amlodipine in mice using maximal electroshock test


  • Pramod D. Shankpal Department of Pharmacology, Topiwala National Medical College and BYL Nair Charitable Hospital, Mumbai, Maharashtra, India
  • Priyanka M. Tawte Department of Pharmacology, Topiwala National Medical College and BYL Nair Charitable Hospital, Mumbai, Maharashtra, India




Calcium channel antagonists, Dihydropyridine, Epilepsy, Seizure


Background: Initial stage of seizure is due to high frequency burst of action potential, caused by long lasting depolarization of the neuronal membrane because of large influx of calcium (Ca) ions into cells. As there is role of calcium channels in the initiation of seizure potential, there may be role of calcium channel antagonists in treatment of epilepsy. Therefore, we assessed the anticonvulsant effect of nimodipine and amlodipine in mice and compared it with phenytoin and sodium valproate.

Methods: A total 42 mice were randomly divided into 7 groups with 6 mice each. Group 1 vehicle (1% CMC), group 2- phenytoin (25 mg/kg) and group 3- sodium valproate (100 mg/kg) p.o. group 4 and 5- nimodipine (4 mg/kg and 8 mg/kg), group 6 and 7- amlodipine (0.7 mg/kg and 1.3 mg/kg) p.o. in 1% CMC. All animals were tested for convulsions with current strength 50 mA for 0.2 seconds, delivered by ear electrodes of electroconvulsiometer. Parameters assessed were presence or absence of convulsions, onset of (latency to) THLE and duration of THLE in seconds, 24 hours mortality.

Results: The difference in percentage of mice being protected from electro convulsions was found to be statistically significant in group 5 (nimodipine 8 mg/kg), group 7 (amlodipine 1.3 mg/kg) as compared to group 1(vehicle control) (p= 0.0152). Onset of (latency to) THLE and duration of THLE, expressed as mean (in seconds) ± standard deviation (SD) and analysed using Kruskal-Wallis non-parametric test showed significant difference in latency to THLE among the groups tested (p value <0.01) and  in duration of THLE among the groups tested (p value <0.01), while post- hoc Dunn’s test showed a statistically significant difference between latency to and duration of THLE in the nimodipine 8 mg/kg and amlodipine 1.3 mg/kg groups as compared to vehicle control group (p<0.01). No mortality seen within 24 hours of testing in any group.

Conclusions: Nimodipine 8 mg/kg and amlodipine 1.3 mg/kg showed significant anticonvulsant activity (absence of tonic hind limb extension), delayed onset of seizures, reduced duration of seizures comparable to positive control (phenytoin and sodium valproate) and more effective than vehicle control.


Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-82.

Lowenstein DH. Seizure and epilepsy. In: Braunwald E, Fauci AS, Hauser SL, eds. Harrison’s Principles of Internal Medicine. 20th edn. New York: McGraw-Hill; 2018:3050-3068.

Czapinski P, Blaszczyk B, Czuczwar SJ. Mechanisms of action of antiepileptic drugs. Current Top Med Chem. 2005;5(1):3-14.

De Lorenzo RJ. A molecular approach to the calcium signal in brain: relationship to synaptic modulation and seizure discharge. Adv Neurol. 1986;44:435-64.

Ramirez-San Juan E, Soriano-Ursua MA, Espinosa-Raya J, Correa-Basurto J, Trujillo-Ferrara JG, Miranda-Ruvalcaba R, et al. Anticonvulsant effects of bis-1,4-dihydropyridines and the probable role of L-type calcium channels suggested by docking simulations. Med Chem Res. 2014;23:5149-59

Larkin JG, Thompson GG, Scobie G, Forrest G, Drennan JE, Brodie MJ. Dihydropyridine calcium antagonists in mice: blood and brain pharmacokinetics and efficacy against pentylenetetrazol seizures. Epilepsia. 1992;33(4):760-9.

Bajracharya SR, Sathyanarayana Rao KN. Antiepileptic effects of amlodipine in mice. J Inst Med. 2016;38(2-3):116-20

Mohamed Abdel GH, Ali DM. Antiepileptic action of amlodipine on maximal electroshock induced seizures in mice. Nat J Physiol Pharm Pharmacol. 2014;4(3):201-7.

Khanna N, Bhalla S, Verma V, Sharma KK. Modulatory effects of nifedipine and nimodipine in experimental convulsions. Indian J Pharmacol. 2000;32(6):347-52.

Jain S, Bharal N, Mediratta PK, Sharma KK. Trimetazidine exerts protection against increasing current electroshock seizure test in mice. Seizure. 2010;19(5):300-2.

Sreedharan N, Rao PG, Rau NR, Shankar PR. Antihypertensive prescribing preferences in three South Indian Hospitals: cost analysis, physicians perspectives and emerging trends. Int J Clin Pharmacol Therap. 2011;49(4):277.

Siddiqui N, Pandeya SN. Anticonvulsant and hypnotic activities of isodithiobiurets and 1, 2, 4-dithiazolines. Indian J Pharmacol. 1992;24(3):171.

Lotarski S, Hain H, Peterson J, Galvin S, Strenkowski B, Donevan S, et al. Anticonvulsant activity of pregabalin in the maximal electroshock-induced seizure assay in α2δ1 (R217A) and α2δ2 (R279A) mouse mutants. Epileps Res. 2014;108(5):833-42.

Bhuvaneshwari. Effect of nimodipine and diclofenac in experimentally induced convulsions using INH and electro convulsometer in rats and mice. J Drug Deliv Therap. 2015; 5(1):61-4.

Vogel HG. Psychotropic and Neurotropic Activity. In: Drug Discovery and Evaluation: Pharmacological Assays. 3rd edn. Vol 1. Berlin: Springer; 2008:396.

Khosla P, Pandhi P. Anticonvulsant effect of nimodipine alone and in combination with diazepam and phenytoin in a mouse model of status epilepticus. Methods Find Exp Clin Pharmacol. 2000;22:731-6.

Phatak AM, Hotwani JH, Deshmukh Kiran R, Panchal SS, Naik MS. Cost analysis of long established and newer oral antiepileptic drugs available in The Indian Market. Int J Med Res Health Sci. 2015;4(4):744-8.

Tartara A, Galimberti CA, Manniv R, Pariettit L, Zucca C, Baasch H, et al. Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients. Br J Clin Pharmacol. 1991;32:335-40.

Langley MS, Sorkin EM. Nimodipine. Drugs. 1989;37(5):669-99.

Uchida S, Yamada S, Nagai K, Deguchi Y, Kimura R. Brain pharmacokinetics and in vivo receptor binding of 1, 4-dihydropyridine calcium channel antagonists. Life Sci. 1997;61(21):2083-90.

Middlemiss DN, Spedding M. A functional correlate for the dihydropyridine binding site in rat brain. Nature. 1985;314(6006):94.

Nordström ÖI, Braesch‐Andersen ST, Bartfai T. Dopamine release is enhanced while acetylcholine release is inhibited by nimodipine (Bay e 9736). Acta Physiol Scand. 1986;126(1):115-9.

Kato T, Otsu Y, Furune Y, Yamamoto T. Different effects of L-, N- and T-type calcium channel blockers on striatal dopamine release measured by microdialysis in freely moving rats. Neurochem Int. 1992;21:99-107.

Pileblad E, Carlsson A. The Ca2+-antagonist nimodipine decreases the Ca2+agonist Bay K 8644 increases catecholamine synthesis in mouse brain. Neuropharmacology. 1987;26:101-5.

Rachana PR, Anuradha HV. Anti-hypertensive prescribing patterns and cost analysis for primary hypertension: a retrospective study. J Clin Diagn Res. 2014;8(9):HC19.

Ohman J. Hypertension as a risk factor for epilepsy after aneurysmal subarachnoid hemorrhage and surgery. Neurosurgery. 1990;27(4):578-81.




How to Cite

Shankpal, P. D., & Tawte, P. M. (2021). Evaluation of the anticonvulsant effect of nimodipine and amlodipine in mice using maximal electroshock test. International Journal of Basic & Clinical Pharmacology, 10(4), 317–323. https://doi.org/10.18203/2319-2003.ijbcp20211009



Original Research Articles