ABSTRACT
BACKGROUND: Epilepsy is one common neurological disorder requiring newer targets and newer drugs for its efficient management. In the recent days brain renin angiotensin system has gained immense importance because of its involvement in seizure regulation. OBJECTIVE: To evaluate and compare antiepileptic activity of different doses olmesartan and telmisartan on MES and PTZ induced seizure models. MATERIALS AND METHODS: Swiss albino mice weighing around 25-30g of either sex were divided into 6 groups: Control ( Distilled Water- 10ml/kg), Standard - Sodium valproate (40mg/kg), O1 - Olmesartan (2.5mg/kg), O2 - Olmesartan (5mg/kg), T1 - Telmisartan (5mg/kg), T2 - Telmisartan (10mg/kg). After 1hour of administration of control , test and standard drugs (orally), convulsions were induced by administering PTZ (70mg/kg - i.p.) in PTZ model. Seizure latency was the parameter recorded. In MES model, suppression of tonic hind limb extension was taken as measure of efficacy. RESULT: The results were analysed by one-way-ANOVA followed by Bonferroni's multiple comparison test. In MES test, dose dependently olmesartan and telmisartan significantly reduced the duration of tonic hindlimb extension in comparison to control (p<0.05). T2 - 9 + 0.89secs significantly reduced the tonic hind limb extension compared to other test groups (p<0.05). The percentage inhibition of seizure was T2-44.3%, O2-28.2%, T1-17.5%, O1- 12.3% respectively. In PTZ test, dose dependently olmesartan and telmisartan produced significant increase in seizure latency (p<0.05). T2 - 206.6+9.83secs significantly increased seizure latency compared to other test groups (p<0.05). Percentage protection from seizure is T2-52.6%, O2- 45.13%, T1- 37.5%, O1- 38.4% respectively. CONCLUSION: AT1 receptor antagonist, telmisartan and olmesartan in a dose dependent manner showed increase in antiepileptic activity. Temisartan at higher dose produced significant antiepileptic activity in comparison to olmesartan.
ABSTRACT
BACKGROUND: Carvedilol is a commonly used drug in hypertension, congestive heart failure in diabetics. It has moderate calcium channel blocking property in addition to α1 and non selective ß antagonistic activity. Though some studies bring forth the beneficial effects of Carvedilol in cardiovascular comorbidities in diabetes, there is no consensus on its effects on glycaemic levels. AIMS: To evaluate the effect of oral Carvedilol administration for 5 days on blood glucose levels in normal albino rats through Oral Glucose Tolerance Test. MATERIAL AND METHODS: Twelve adult albino rats of either sex weighing between 150 - 200 g were selected from central animal facility and randomly divided into 2 groups - Control [Distilled water (1ml/rat orally)] and Test (0.8mg/kg body weight orally) and the respective drugs were administered over 5 days. Following overnight fasting, on the fifth day 1 hour after the last dose of the respective drug, OGTT was performed. The CBG (Capillary Blood Glucose) levels were measured at 0 min, glucose (2g/kg body weight) dissolved in water was administered to all the rats orally. The blood sample from tail vein (obtained by tail snipping) at 60 and 150 minutes were analysed for CBG levels using a standardized glucometer. STATISTICAL ANALYSIS: Data was presented as Mean ± SEM. One way ANOVA, independent samples t-test, non-parametric tests, percentages and cross tabs were used in the analysis of data within the same group and between different groups when required. RESULTS: Carvedilol group showed higher CBG levels at all time intervals of OGTT as compared to the Control group i.e., 0, 60 and 150 minutes, the highest being (103.8±5.029 )mg/dl at 60 minutes and was statistically significant. Carvedilol group however showed lesser inter-interval variation compared to the Control group at the same time intervals respectively but was statistically insignificant. CONCLUSIONS: Carvedilol has hyperglycaemic potential when given orally for 5 days in normal albino rats. Though it may be beneficial in diabetics for various comorbid conditions, the glycaemic control may worsen during its use in subjects with prediabetes, diabetes, high risk diabetes.
