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Methylxanthines pp 251–266Cite as

Methylxanthines, Seizures, and Excitotoxicity

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 200))

Abstract

Clinical evidence, in particular the wide use of theophylline as a bronchodilator, suggests that methylxanthines can cause seizures in patients without known underlying epilepsy. Theophylline is also known to be an added risk factor for seizure exacerbation in patients with epilepsy. The proconvulsant activity of methylxanthines can best be explained by their antagonizing the brain’s own anticonvulsant adenosine. Recent evidence suggests that adenosine dysfunction is a pathological hallmark of epilepsy contributing to seizure generation and seizure spread. Conversely, adenosine augmentation therapies are effective in seizure suppression and prevention, whereas adenosine receptor antagonists such as methylxanthines generally exacerbate seizures. The impact of the methylxanthines caffeine and theophylline on seizures and excitotoxicity depends on timing, dose, and acute versus chronic use. New findings suggest a role of free radicals in theophylline-induced seizures, and adenosine-independent mechanisms for seizure generation have been proposed.

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Acknowledgements

The work of the author is supported by grants R01NS058780, R01NS061844, R01MH083973, R21NS057475-01, and R21NS057538-01 from the National Institutes of Health (NIH), from Citizens United in Research against Epilepsy (CURE) in collaboration with the Department of Defense (DoD), and from the Legacy Hospital Foundation.

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  1. R.S. Dow Neurobiology Laboratories, Legacy Research, Portland, OR, 97232, USA

    Detlev Boison

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Boison, D. (2011). Methylxanthines, Seizures, and Excitotoxicity. In: Methylxanthines. Handbook of Experimental Pharmacology, vol 200. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13443-2_9

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