Next Article in Journal
Characterization of a Primate Blood-Brain Barrier Co-Culture Model Prepared from Primary Brain Endothelial Cells, Pericytes and Astrocytes
Previous Article in Journal
Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment
Previous Article in Special Issue
Children’s Preferences for Oral Dosage Forms and Their Involvement in Formulation Research via EPTRI (European Paediatric Translational Research Infrastructure)
Article

The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats

1
Department of Developmental Epileptology, Institute of Physiology, Czech Academy of Sciences, 14220 Prague, Czech Republic
2
Department of Rehabilitation and Sport Medicine, 2nd Medical Faculty, Charles University, 15006 Prague, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editors: Nunzio Denora and Rosa Maria Iacobazzi
Pharmaceutics 2021, 13(9), 1482; https://doi.org/10.3390/pharmaceutics13091482
Received: 14 August 2021 / Revised: 12 September 2021 / Accepted: 13 September 2021 / Published: 16 September 2021
The GluN2B subunit of NMDA receptors represents a perspective therapeutic target in various CNS pathologies, including epilepsy. Because of its predominant expression in the immature brain, selective GluN2B antagonists are expected to be more effective early in postnatal development. The aim of this study was to identify age-dependent differences in the anticonvulsant activity of the GluN2B-selective antagonist Ro 25-6981 and assess the safety of this drug for the developing brain. Anticonvulsant activity of Ro 25-6981 (1, 3, and 10 mg/kg) was tested in a pentylenetetrazol (PTZ) model in infantile (12-day-old, P12) and juvenile (25-day-old, P25) rats. Ro 25-6981 (1 or 3 mg/kg/day) was administered from P7 till P11 to assess safety for the developing brain. Animals were then tested repeatedly in a battery of behavioral tests focusing on sensorimotor development, cognition, and emotionality till adulthood. Effects of early exposure to Ro 25-6981 on later seizure susceptibility were tested in the PTZ model. Ro 25-6981 was effective against PTZ-induced seizures in infantile rats, specifically suppressing the tonic phase of the generalized tonic–clonic seizures, but it failed in juveniles. Neither sensorimotor development nor cognitive abilities and emotionality were affected by early-life exposure to Ro 25-6981. Treatment cessation did not affect later seizure susceptibility. Our data are in line with the maturational gradient of the GluN2B-subunit of NMDA receptors and demonstrate developmental differences in the anti-seizure activity of the GluN2B-selective antagonist and its safety for the developing brain. View Full-Text
Keywords: development; GluN2B-selective antagonist; Ro 25-6981; anti-seizure effects; motor performance; memory; immature rats development; GluN2B-selective antagonist; Ro 25-6981; anti-seizure effects; motor performance; memory; immature rats
Show Figures

Figure 1

MDPI and ACS Style

Mareš, P.; Kozlová, L.; Mikulecká, A.; Kubová, H. The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats. Pharmaceutics 2021, 13, 1482. https://doi.org/10.3390/pharmaceutics13091482

AMA Style

Mareš P, Kozlová L, Mikulecká A, Kubová H. The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats. Pharmaceutics. 2021; 13(9):1482. https://doi.org/10.3390/pharmaceutics13091482

Chicago/Turabian Style

Mareš, Pavel, Lucie Kozlová, Anna Mikulecká, and Hana Kubová. 2021. "The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats" Pharmaceutics 13, no. 9: 1482. https://doi.org/10.3390/pharmaceutics13091482

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop