Determining the Evaluation of Anticonvulsant Activity of Angiotensin Receptor Antagonists in an Animal Model
Background: In clinical practise, epilepsy is a frequent chronic condition, and some research suggests that the renin-angiotensin system in the brain is involved in seizure upregulation.
The goal of this study was to discover if AT1 receptor antagonists for angiotensin II have anticonvulsant activity in experimental mice.
Methods: Mice were treated intraperitoneally Losartan (50 mg/kg), Telmisartan (30 mg/kg), and Candesartan (20 mg/kg) and their anticonvulsant activity was tested using the maximum electroshock (MES) and Pentylenetetrazol induced seizures (PTZ) seizure procedures. The benchmark for the MES method was phenytoin, whereas the standard for the PTZ method was diazepam. The inverted screen test and spontaneous motor activity with a digital actophotometer were used to detect motor impairment.
Losartan’s anticonvulsant efficacy was demonstrated in both the MES and PTZ models. Telmisartan and Candesartan had an anticonvulsant effect in MES-induced seizures, but not in Pentylenetetrazol-induced seizures. Losartan, at a dose of 50 mg/kg, significantly reduced the mean latency to convulsion (p0.01) and the mean number of convulsions (p0.05) in mice. With Telmisartan and Candesartan at doses of 30 mg/kg and 20 mg/kg, respectively, the mean latency to convulsion was significantly prolonged (p0.05). Any of the test drugs, such as angiotensin receptor antagonists, did not cause significant motor impairment.
Conclusions: Angiotensin receptor antagonists Losartan, Telmisartan, and Candesartan have been found to exhibit anticonvulsant effect in PTZ and MES seizure models. More study is needed to test it in a range of other anticonvulsant animal models because the particular mechanism of action of its anticonvulsant efficacy is unknown.
Author (S) Details
Asha Dattatraye Jadhav
Department of Pharmacology, Dr Vithalrao Vikhe Patil Medical College and Hospital, Ahmednagar, Maharashtra, India.
Rakesh Jadhav
Department of Pharmacology, SRTR Govt. Medical College Ambajogai, Beed Maharashtra, India.
Sudhir Padwal
Department of Pharmacology, SRTR Govt. Medical College Ambajogai, Beed Maharashtra, India.
Anand Kale
Department of Pharmacology, SRTR Govt. Medical College Ambajogai, Beed Maharashtra, India.
Swapnil Jadhav
Department of Pharmacology, GMC Miraj, Maharashtra, India.
Prakashchandra Gade
Department of Pharmacology, Dr Vithalrao Vikhe Patil Medical College and Hospital, Ahmednagar, Maharashtra, India.
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