An update of cyclooxygenase (COX)-inhibitors in epilepsy disorders

ABSTRACT

Introduction: Neuroinflammation has a critical role in brain disorders. Cyclooxygenase (COX) is one of the principal drug targets for the reduction of neuroinflammation; however, studies have yielded mixed results for COX-inhibitors in the treatment of diverse acute and chronic models of epilepsy.

Areas covered: The article covers the effects of COX-inhibitors in epilepsy disorders. A considerable emphasis has been placed on the antiepileptic and ‘disease-modifying’ properties of COX-1 and COX-2 inhibitors in various preclinical epilepsy models.

Expert opinion: The effect of COX-inhibitors on epilepsy is inconclusive. Studies have indicated beneficial effects in preclinical models; however, proconvulsant or no effects have also been observed. These molecules may have a bidirectional role with early neuroprotective and delayed neurotoxic effects. Further systematic preclinical studies to establish the use of COX-inhibitors in epilepsy are necessary.

KEYWORDS:

• Cyclooxygenase (COX)
• epilepsy
• spontaneous recurrent seizures
• antiepileptic
• antiepileptogenic
• proconvulsant

Article highlights

1. COX enzyme (COX-1 and COX-2 isoforms) is expressed in the CNS and is involved in the pathophysiology of various brain disorders, including epilepsy.

2. Preclinical investigations have demonstrated the prevention of, or reduction of severity of seizure episodes; however, proconvulsant and no effect have also been observed. There is a need for further well-organized preclinical investigations.

3. COX-2 inhibitors may prevent pharmacoresistance in various animal models of epilepsy.

4. The chronic use of COX-inhibitors is associated with side effects and adverse drug reactions.

5. The discovery and development of novel and safe COX-inhibitors for the treatment of epilepsy is an important but very challenging area of research.

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Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.