The Impact of Brivaracetam on Cognitive Processes and Anxiety in Various Experimental Models

Overview

Journal Pharmacol Rep

Specialty Pharmacology

Date 2024 Jan 5

PMID 38182968

Authors

Ewa Zwierzynska

Boguslawa Pietrzak

Affiliations

Soon will be listed here.

Abstract

Background: Memory deficits and anxiety symptoms are undesirable effects that occur in epilepsy patients. They may be associated with the pathophysiology of the disease but also with anticonvulsant therapy. Brivaracetam (BRV) is one of the newest antiseizure drugs. It acts as a ligand for synaptic vesicle glycoprotein 2A (SV2A), which may play a significant role in cognitive processes. Although BRV has a favorable safety profile, its central side effects remain unclear. Hence, this study aimed to evaluate the effect of BRV on various types of memory and anxiety in rats.

Methods: BRV was given to adult male Wistar rats (n = 80) via gastric tube as a single dose (6 mg/kg or 20 mg/kg) or chronically (6 mg/kg). The effect of the drug on spatial memory was evaluated in the Morris water maze (MWM), fear-learning by passive avoidance (PA), and recognition memory with novel object recognition (NOR). The elevated plus maze (EPM) was used to assess anxiety-like behaviors.

Results: The impact of BRV on memory is dose-dependent and mainly high doses may alter retrieval memory and fear-learning. Sub-chronic administration also impaired retrieval and spatial memory in animals. Moreover, chronic BRV may increase anxiety levels in rats but did not affect recognition memory.

Conclusions: BRV may cause transient memory deficits as well as anxiety disturbances. However, the results are varied and depend on the type of memory, used dose, and duration of administration.

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References

Nissenkorn A, Tzadok M, Bar-Yosef O, Ben-Zeev B . Treatment with brivaracetam in children - The experience of a pediatric epilepsy center. Epilepsy Behav. 2019; 101(Pt A):106541. DOI: 10.1016/j.yebeh.2019.106541. View

Motamedi G, Meador K . Antiepileptic drugs and memory. Epilepsy Behav. 2004; 5(4):435-9. DOI: 10.1016/j.yebeh.2004.03.006. View

Zahnert F, Krause K, Immisch I, Habermehl L, Gorny I, Chmielewska I . Brivaracetam in the Treatment of Patients with Epilepsy-First Clinical Experiences. Front Neurol. 2018; 9:38. PMC: 5808159. DOI: 10.3389/fneur.2018.00038. View

Margineanu D, Klitgaard H . Brivaracetam inhibits spreading depression in rat neocortical slices in vitro. Seizure. 2009; 18(6):453-6. DOI: 10.1016/j.seizure.2009.01.002. View

Fang Y, Si X, Wang J, Wang Z, Chen Y, Liu Y . Alzheimer Disease and Epilepsy: A Mendelian Randomization Study. Neurology. 2023; 101(4):e399-e409. PMC: 10435057. DOI: 10.1212/WNL.0000000000207423. View

Detrait E, Leclercq K, Loscher W, Potschka H, Niespodziany I, Hanon E . Brivaracetam does not alter spatial learning and memory in both normal and amygdala-kindled rats. Epilepsy Res. 2010; 91(1):74-83. DOI: 10.1016/j.eplepsyres.2010.06.014. View

Nau A, Mwape K, Wiefek J, Schmidt K, Abatih E, Dorny P . Cognitive impairment and quality of life of people with epilepsy and neurocysticercosis in Zambia. Epilepsy Behav. 2017; 80:354-359. DOI: 10.1016/j.yebeh.2017.10.042. View

Serrano M, Bartholome O, Van Den Ackerveken P, Ferrara A, Rogister B, Plenevaux A . Anxiety-like features and spatial memory problems as a consequence of hippocampal SV2A expression. PLoS One. 2019; 14(6):e0217882. PMC: 6550411. DOI: 10.1371/journal.pone.0217882. View

Niespodziany I, Rigo J, Moonen G, Matagne A, Klitgaard H, Wolff C . Brivaracetam does not modulate ionotropic channels activated by glutamate, γ-aminobutyric acid, and glycine in hippocampal neurons. Epilepsia. 2017; 58(11):e157-e161. DOI: 10.1111/epi.13890. View

10.

Nygaard H, Kaufman A, Sekine-Konno T, Huh L, Going H, Feldman S . Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer's disease mouse model. Alzheimers Res Ther. 2015; 7(1):25. PMC: 4419386. DOI: 10.1186/s13195-015-0110-9. View

11.

Meador K, Gevins A, Leese P, Otoul C, Loring D . Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam. Epilepsia. 2010; 52(2):264-72. DOI: 10.1111/j.1528-1167.2010.02746.x. View

12.

Zhu L, Chen D, Chen T, Xu D, Chen S, Liu L . The adverse event profile of brivaracetam: A meta-analysis of randomized controlled trials. Seizure. 2016; 45:7-16. DOI: 10.1016/j.seizure.2016.11.008. View

13.

OBrien T, Borghs S, He Q, Schulz A, Yates S, Biton V . Long-term safety, efficacy, and quality of life outcomes with adjunctive brivaracetam treatment at individualized doses in patients with epilepsy: An up to 11-year, open-label, follow-up trial. Epilepsia. 2020; 61(4):636-646. PMC: 7384045. DOI: 10.1111/epi.16484. View

14.

Niquet J, Suchomelova L, Thompson K, Klitgaard H, Matagne A, Wasterlain C . Acute and long-term effects of brivaracetam and brivaracetam-diazepam combinations in an experimental model of status epilepticus. Epilepsia. 2017; 58(7):1199-1207. PMC: 5508597. DOI: 10.1111/epi.13787. View

15.

Lopatynska-Mazurek M, Pankowska A, Gibula-Tarlowska E, Pietura R, Kotlinska J . Rapamycin Improves Recognition Memory and Normalizes Amino-Acids and Amines Levels in the Hippocampal Dentate Gyrus in Adult Rats Exposed to Ethanol during the Neonatal Period. Biomolecules. 2021; 11(3). PMC: 7997340. DOI: 10.3390/biom11030362. View

16.

Gillard M, Fuks B, Leclercq K, Matagne A . Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol. 2011; 664(1-3):36-44. DOI: 10.1016/j.ejphar.2011.04.064. View

17.

Ge Y, Lin Y, Bi Q, Chen Y . Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats. Curr Neurovasc Res. 2020; 17(4):354-360. DOI: 10.2174/1567202617666200514114917. View

18.

Sanon N, Gagne J, Wolf D, Aboulamer S, Bosoi C, Simard A . Favorable adverse effect profile of brivaracetam vs levetiracetam in a preclinical model. Epilepsy Behav. 2017; 79:117-125. DOI: 10.1016/j.yebeh.2017.11.019. View

19.

Cetiner M, Aydin H . Demonstration of the effect of brivaracetam on an experimental epilepsy model. Turk J Med Sci. 2018; 48(6):1315-1320. DOI: 10.3906/sag-1806-236. View

20.

Sargentini-Maier M, Espie P, Coquette A, Stockis A . Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab Dispos. 2007; 36(1):36-45. DOI: 10.1124/dmd.107.017129. View