ANTIEPILEPTIC EFFECT OF TELMISARTAN AND VALSARTAN ALONE AND IN COMBINATION WITH ETHOSUXIMIDE ON PENTYLENETETRAZOL INDUCED EXPERIMENTAL MODEL OF EPILEPSY IN ALBINO MICEAbstract
Epilepsy is a common neurological disorder in clinical practice requiring newer targets for its efficient treatment. Recently, brain renin-angiotensin system has gained immense importance because of its involvement in seizure regulation. Hence, the present study was planned to evaluate whether angiotensin II AT1 receptor antagonists possess anticonvulsant activity in experimental animals. Forty- eight Swiss albino mice were divided into 8 groups: Control – distilled water (5ml/kg), Standard – ethosuximide 200mg/kg, T1- telmisartan 5mg/kg, T2- telmisartan 8mg/kg, V1- valsartan 10mg/kg, V2- valsartan 20mg/kg, E+T2- ethosuximide 200mg/kg+ telmisartan 8mg/kg, E+V2- ethosuximide 200mg/kg+ valsartan 20mg/kg. After 1 hour of administration of control, test and standard drugs intraperitonally, convulsions were induced by administering pentylenetetrazol (60mg/kg- s.c). The time of onset of myoclonic spasm and clonic convulsion were the parameters recorded. The results were analysed by one-way- ANOVA followed by Dunnett’s t test. Telmisartan 8mg/kg, valsartan 10mg/kg, valsartan 20mg/kg significantly increased the latency of onset of myoclonic spasm and clonic convulsion (p< 0.05) as compared to control. The combinations of (ethosuximide + telmisartan 8mg/kg) and (ethosuximide + valsartan 20mg/kg) also significantly increased the latencies of onset of myoclonic spasm and clonic convulsion (p<0.05) as compared to control. Conclusively, angiotensin receptor antagonist viz. telmisartan and valsartan showed anticonvulsant activity in PTZ seizure models. Both telmisartan and valsartan potentiated the antiepileptic activity of ethosuximide. So, dose of ethosuximide can be reduced in epileptic patients receiving telmisartan or valsartan for other clinical conditions.
Premi Devi Moirangthem * and Babycha Laishram
Department of Pharmacology, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India.
16 January 2023
23 March 2023
25 April 2023
01 September 2023