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Department of Neurology

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Nervous System Diseases | Neurology


Background and Purpose: Accumulating evidence suggest that lenalidomide, a structural analog of thalidomide, has neuro-modulatory and neuroprotective properties. In the present study, we investigated effects of acute administration of lenalidomide on clonic seizure threshold in mice induced by pentylenetetrazole (PTZ) and possible role of N-methyl-D-aspartic acid receptor (NMDAR) and nitric oxide (NO) pathway.

Methods: We have utilized a clonic model of seizure in NMRI mice induced by PTZ to evaluate the potential effect of lenalidomide on seizure threshold. Different doses of lenalidomide (5, 10, 20, and 50 mg/kg, intraperitoneal [i.p.]) were administered 1 hour before PTZ. To evaluate probable role of NMDAR/NO signaling, the non-selective NO synthase inhibitor L-N (G)-nitroarginine methyl ester (L-NAME; 10 mg/kg, i.p.), neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI; 30 mg/kg, i.p.), selective inducible NOS inhibitor aminoguanidine (AG; 100 mg/kg, i.p.), selective NMDAR antagonist MK-801 (0.01 mg/kg, i.p.), and selective NMDAR agonist D-serine (30 mg/kg, i.p.) were injected 15 minutes before lenalidomide.

Results: Lenalidomide at 10 and 20 mg/kg significantly elevated the PTZ-induced seizure thresholds. Interestingly, L-NAME (10 mg/kg, i.p), 7-NI (30 mg/kg, i.p), and AG (100 mg/kg, i.p) reversed the anticonvulsive effect of lenalidomide (10 mg/kg). Moreover, treatment with the NMDAR agonist D-serine (30 mg/kg, i.p.) did not alter the anticonvulsive properties of lenalidomide (10 mg/kg, i.p). However, the NMDAR antagonist MK-801 (0.01 mg/kg, i.p) significantly reversed the anticonvulsive effects of lenalidomide (10 mg/kg).

Conclusions: Our study demonstrated a role for the NMDAR/NO pathway in the anticonvulsive effects of lenalidomide on the PTZ-induced clonic seizures in mice.


Lenalidomide, Mice, N-methyl-D-aspartate receptors, Nitric oxide synthase

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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



Dafe EA, Rahimi N, Javadian N, Dejban P, Komeili M, Modabberi S, Ghasemi M, Dehpour AR. Effect of Lenalidomide on Pentylenetetrazole-Induced Clonic Seizure Threshold in Mice: A Role for N-Methyl-D-Aspartic Acid Receptor/Nitric Oxide Pathway. J Epilepsy Res. 2021 Jun 30;11(1):6-13. doi: 10.14581/jer.21002. PMID: 34395218; PMCID: PMC8357552. Link to article on publisher's site

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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