Caffeine impairs anticonvulsant effects of levetiracetam in the maximal electroshock seizure threshold test in mice.

Q3 Pharmacology, Toxicology and Pharmaceutics Journal of Basic and Clinical Physiology and Pharmacology Pub Date : 2023-05-01 DOI:10.1515/jbcpp-2022-0224
Roman Chwedorowicz, Krzysztof Łukawski, Grzegorz Raszewski, Stanisław J Czuczwar
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Abstract

Objectives: Caffeine is the most widely used psychoactive substance in the world. Animal studies indicate that acute caffeine exposure at high doses may induce seizures and diminish the anticonvulsant activity of antiepileptic drugs (AEDs) at much lower doses. The aim of the current study was to assess the effect of caffeine on the anticonvulsant action of levetiracetam (LEV) and vigabatrin (VGB).

Methods: The anticonvulsant activity of LEV and VGB was examined in the maximal electroshock seizure threshold test in mice (MEST test). All drugs were administered intraperitoneally by single injections, and caffeine was applied at doses capable of interfering with AEDs. Effects of caffeine exposure on AEDs were also investigated in tests of memory and motor performance.

Results: Caffeine reduced the protective effect of LEV against electroconvulsions. Total brain concentration of LEV was unaffected by caffeine as well as inversely; LEV had no significant impact on the brain caffeine concentration, suggesting a pharmacodynamic nature of the interaction between LEV and caffeine in the MEST test. VGB at applied doses did not affect the convulsive threshold. Administration of VGB, but not LEV, alone or in combination with caffeine, impaired memory retention. In the chimney test, the combined treatment with AEDs and caffeine did not cause motor coordination impairment.

Conclusions: It is suggested that caffeine may negatively affect the anticonvulsant action of LEV in patients with epilepsy.

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在小鼠最大电休克发作阈值试验中,咖啡因损害左乙拉西坦的抗惊厥作用。
目的:咖啡因是世界上使用最广泛的精神活性物质。动物研究表明,急性高剂量咖啡因暴露可能诱发癫痫发作,并降低低剂量抗癫痫药物(AEDs)的抗惊厥活性。本研究的目的是评估咖啡因对左乙拉西坦(LEV)和维加巴林(VGB)抗惊厥作用的影响。方法:采用小鼠最大电休克发作阈值试验(MEST)检测LEV和VGB的抗惊厥活性。所有药物均通过腹腔单次注射给药,咖啡因的剂量足以干扰aed。在记忆和运动表现测试中也研究了咖啡因暴露对抗癫痫药的影响。结果:咖啡因降低了LEV对电惊厥的保护作用。脑内LEV总浓度不受咖啡因影响,反之亦然;LEV对脑内咖啡因浓度无显著影响,提示在MEST测试中LEV与咖啡因的相互作用具有药效学性质。施加剂量的VGB不影响惊厥阈值。单独或与咖啡因联合服用VGB,而不是LEV,会损害记忆保留。在烟囱试验中,AEDs和咖啡因联合治疗没有引起运动协调障碍。结论:咖啡因可能对LEV在癫痫患者中的抗惊厥作用产生负面影响。
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来源期刊
Journal of Basic and Clinical Physiology and Pharmacology
Journal of Basic and Clinical Physiology and Pharmacology Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
3.90
自引率
0.00%
发文量
53
期刊介绍: The Journal of Basic and Clinical Physiology and Pharmacology (JBCPP) is a peer-reviewed bi-monthly published journal in experimental medicine. JBCPP publishes novel research in the physiological and pharmacological sciences, including brain research; cardiovascular-pulmonary interactions; exercise; thermal control; haematology; immune response; inflammation; metabolism; oxidative stress; and phytotherapy. As the borders between physiology, pharmacology and biochemistry become increasingly blurred, we also welcome papers using cutting-edge techniques in cellular and/or molecular biology to link descriptive or behavioral studies with cellular and molecular mechanisms underlying the integrative processes. Topics: Behavior and Neuroprotection, Reproduction, Genotoxicity and Cytotoxicity, Vascular Conditions, Cardiovascular Function, Cardiovascular-Pulmonary Interactions, Oxidative Stress, Metabolism, Immune Response, Hematological Profile, Inflammation, Infection, Phytotherapy.
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