The Role of Angiotensin Receptor Blockers in Treating Epilepsy: a Review

Overview

Journal Neurol Sci

Specialty Neurology

Date 2023 Dec 11

PMID 38079018

Authors

Taha Gul Shaikh

Syeda Fatima Saba Hasan

Hiba Ahmed

Amal Iqbal Kazi

Ruhma Mansoor

Affiliations

Soon will be listed here.

Abstract

Epilepsy is a chronic brain disease with a global prevalence of 70 million people. According to the World Health Organization, roughly 5 million new cases are diagnosed every year. Anti-seizure drugs are the treatment of choice. However, in roughly one third of the patients, these drugs fail to produce the desired effect. As a result, finding novel treatments for epilepsy becomes inevitable. Recently, angiotensin receptor blockers have been proposed as a treatment to reduce the over-excitation of neurons in epilepsy. For this purpose, we conducted a review using Medline/PubMed and Google Scholar using the relevant search terms and extracted the relevant data in a table. Our review suggests that this novel approach has a very high potential to treat epilepsy, especially in those patients who fail to respond to conventional treatment options. However, more extensive and human-based trials should be conducted to reach a decisive conclusion. Nevertheless, the use of ARBs in patients with epilepsy should be carefully monitored keeping the adverse effects in mind.

References

Thijs R, Surges R, OBrien T, Sander J . Epilepsy in adults. Lancet. 2019; 393(10172):689-701. DOI: 10.1016/S0140-6736(18)32596-0. View

Falco-Walter J . Epilepsy-Definition, Classification, Pathophysiology, and Epidemiology. Semin Neurol. 2020; 40(6):617-623. DOI: 10.1055/s-0040-1718719. View

Perucca P, Scheffer I, Kiley M . The management of epilepsy in children and adults. Med J Aust. 2018; 208(5):226-233. DOI: 10.5694/mja17.00951. View

Mesraoua B, Deleu D, Kullmann D, Shetty A, Boon P, Perucca E . Novel therapies for epilepsy in the pipeline. Epilepsy Behav. 2019; 97:282-290. DOI: 10.1016/j.yebeh.2019.04.042. View

Doege C, Luedde M, Kostev K . Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension. JAMA Neurol. 2022; 79(12):1296-1302. PMC: 9577879. DOI: 10.1001/jamaneurol.2022.3413. View

Patel S, Rauf A, Khan H, Abu-Izneid T . Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies. Biomed Pharmacother. 2017; 94:317-325. DOI: 10.1016/j.biopha.2017.07.091. View

Wright J, Harding J . Brain renin-angiotensin--a new look at an old system. Prog Neurobiol. 2011; 95(1):49-67. DOI: 10.1016/j.pneurobio.2011.07.001. View

Singh K, Karnik S . Angiotensin Receptors: Structure, Function, Signaling and Clinical Applications. J Cell Signal (Los Angel). 2016; 1(2). PMC: 4976824. DOI: 10.4172/jcs.1000111. View

Rodriguez-Perez A, Sucunza D, Pedrosa M, Garrido-Gil P, Kulisevsky J, Lanciego J . Angiotensin Type 1 Receptor Antagonists Protect Against Alpha-Synuclein-Induced Neuroinflammation and Dopaminergic Neuron Death. Neurotherapeutics. 2018; 15(4):1063-1081. PMC: 6277291. DOI: 10.1007/s13311-018-0646-z. View

10.

Qu L, Pan C, He S, Lang B, Gao G, Wang X . The Ras Superfamily of Small GTPases in Non-neoplastic Cerebral Diseases. Front Mol Neurosci. 2019; 12:121. PMC: 6555388. DOI: 10.3389/fnmol.2019.00121. View

11.

Gouveia T, Frangiotti M, Vieira de Brito J, de Castro Neto E, Sakata M, Febba A . The levels of renin-angiotensin related components are modified in the hippocampus of rats submitted to pilocarpine model of epilepsy. Neurochem Int. 2012; 61(1):54-62. DOI: 10.1016/j.neuint.2012.04.012. View

12.

Arganaraz G, Konno A, Perosa S, Santiago J, Boim M, Berguio Vidotti D . The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis. Epilepsia. 2008; 49(8):1348-57. DOI: 10.1111/j.1528-1167.2008.01581.x. View

13.

Ivanova N, Tchekalarova J . The Potential Therapeutic Capacity of Inhibiting the Brain Renin-Angiotensin System in the Treatment of Co-Morbid Conditions in Epilepsy. CNS Drugs. 2019; 33(11):1101-1112. DOI: 10.1007/s40263-019-00678-4. View

14.

Tchekalarova J, Ivanova N, Pechlivanova D, Atanasova D, Lazarov N, Kortenska L . Antiepileptogenic and neuroprotective effects of losartan in kainate model of temporal lobe epilepsy. Pharmacol Biochem Behav. 2014; 127:27-36. DOI: 10.1016/j.pbb.2014.10.005. View

15.

Tchekalarova J, Ivanova N, Atanasova D, Pechlivanova D, Lazarov N, Kortenska L . Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy. Cell Mol Neurobiol. 2015; 36(6):927-941. PMC: 11482433. DOI: 10.1007/s10571-015-0278-3. View

16.

Kaschina E, Unger T . Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003; 12(2):70-88. DOI: 10.1080/08037050310001057. View

17.

Tchekalarova J, Loyens E, Smolders I . Effects of AT1 receptor antagonism on kainate-induced seizures and concomitant changes in hippocampal extracellular noradrenaline, serotonin, and dopamine levels in Wistar-Kyoto and spontaneously hypertensive rats. Epilepsy Behav. 2015; 46:66-71. DOI: 10.1016/j.yebeh.2015.03.021. View

18.

Klein P, Friedman A, Hameed M, Kaminski R, Bar-Klein G, Klitgaard H . Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?. Epilepsia. 2020; 61(3):359-386. PMC: 8317585. DOI: 10.1111/epi.16450. View

19.

Reyes-Garcia S, Scorza C, Ortiz-Villatoro N, Cavalheiro E . Losartan fails to suppress epileptiform activity in brain slices from resected tissues of patients with drug resistant epilepsy. J Neurol Sci. 2019; 397:169-171. DOI: 10.1016/j.jns.2019.01.008. View

20.

Russo E, Leo A, Scicchitano F, Donato A, Ferlazzo E, Gasparini S . Cerebral small vessel disease predisposes to temporal lobe epilepsy in spontaneously hypertensive rats. Brain Res Bull. 2017; 130:245-250. DOI: 10.1016/j.brainresbull.2017.02.003. View