Determining the Evaluation of Anticonvulsant Activity of Angiotensin Receptor Antagonists in an Animal Model

Abstract

Background: Epilepsy is a common chronic illness in clinical practise, and some research suggests that the renin-angiotensin system in the brain may be involved in seizure upregulation.

Aims: The purpose of this investigation was to see if angiotensin II AT1 receptor antagonists have anticonvulsant activity in experimental mice.

Methods: Losartan (50 mg/kg), Telmisartan (30 mg/kg), and Candesartan (20 mg/kg) were given intraperitoneally to mice and their anticonvulsant activity was assessed using the maximal electroshock (MES) and Pentylenetetrazol induced seizures (PTZ) seizure techniques. For the MES method, phenytoin was used as the standard, while for the PTZ method, diazepam was used as the standard. Motor impairment of performance was assessed by the inverted screen test and spontaneous motor activity with digital actophotometer.

Results: Losartan's anticonvulsant effectiveness was demonstrated in MES and PTZ models. In MES-induced seizures, Telmisartan and Candesartan showed anticonvulsant effect, but not against Pentylenetetrazol-induced seizures. Losartan at dose 50 mg/kg prolonged the mean latency to convulsion (p<0.01) and mean number of convulsions also significantly reduced (p<0.05) convulsions in the mice.  The mean latency to convulsion was significantly prolonged with Telmisartan and Candesartan at doses of 30 mg/kg and 20 mg/kg, respectively (p<0.05).  There was no substantial motor impairment with any of the test medicines, such as angiotensin receptor antagonists. Conclusions: Losartan, Telmisartan, and Candesartan are angiotensin receptor antagonists that have been shown to have anticonvulsant activity in PTZ and MES seizure models. Because the specific mechanism of action of its anticonvulsant activity is unknown, more research is needed to test it in a variety of other anticonvulsant animal models.