UMMS Affiliation

Department of Neurology

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Document Type



Nervous System Diseases | Neurology


Background and Purpose: Licofelone is a dual 5-lipoxygenase/cyclooxygenase inhibitor, with well-documented anti-inflammatory and analgesic effects, which is used for treatment of osteoarthritis. Recent preclinical studies have also suggested neuroprotective and anti-oxidative properties of this drug in some neurological conditions such as seizure and epilepsy. We have recently demonstrated a role for nitric oxide (NO) signaling in the anti-epileptic activity of licofelone in two seizure models in rodents. Given the important role of N-methyl-D-aspartate receptors (NMDARs) activation in the NO production and its function in the nervous system, in the present study, we further investigated the involvement of NMDAR in the effects of licofelone (1, 3, 5, 10, and 20 mg/kg, intraperitoneal [i.p.]) in an in vivo model of seizure in mice.

Methods: Clonic seizures were induced in male NMRI mice by intravenous administration of pentylenetetrazol (PTZ).

Results: Acute administration of licofelone exerted anticonvulsant effects at 10 (p < 0.01) and 20 mg/kg (p < 0.001). A combined treatment with sub-effective doses of the selective NMDAR antagonist MK-801 (0.05 mg/kg, i.p.) and licofelone (5 mg/kg, i.p.) significantly (p < 0.001) exerted an anticonvulsant effect on the PTZ-induced clonic seizures in mice. Notably, pre-treatment with the NMDAR co-agonist D-serine (30 mg/kg, i.p.) partially hindered the anticonvulsant effects of licofelone (20 mg/kg).

Conclusions: Our data suggest a possible role for the NMDAR in the anticonvulsant effects of licofelone on the clonic seizures induced by PTZ in mice.


Licofelone, Mice, N-methyl-D-aspartate receptor, Pentylenetetrazole, Seizures

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Copyright © 2021 Korean Epilepsy Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version



Gholizadeh R, Abdolmaleki Z, Bahremand T, Ghasemi M, Gharghabi M, Dehpour AR. Involvement of N-Methyl-D-Aspartate Receptors in the Anticonvulsive Effects of Licofelone on Pentylenetetrazole-Induced Clonic Seizure in Mice. J Epilepsy Res. 2021 Jun 30;11(1):14-21. doi: 10.14581/jer.21003. PMID: 34395219; PMCID: PMC8357553. Link to article on publisher's site

Journal/Book/Conference Title

Journal of epilepsy research

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Creative Commons License

Creative Commons Attribution-Noncommercial 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License