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RESEARCH PAPER
Interactions of C-11 with selected antiseizure medications in the mouse 6 Hz psychomotor seizure model – an isobolographic analysis
1
Department of Experimental Pharmacology, Institute of Rural Health, Lublin, Poland
2
Department of Occupational Medicine, Medical University, Lublin, Poland
3
Department of Medicinal Chemistry, Jagiellonian University Medical College, Kraków, Poland
Corresponding author
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Currently, polytherapy with two or more antiseizure medications (ASMs) remains one of the therapeutic options for patients with drug-resistant epilepsy. C-11, a pyrrolidine-2,5-dione derivative with previously demonstrated antiseizure activity, has been proposed as a potential adjunct compound. The aim of the present study is to characterize the type of interactions between C-11 and two clinically used ASMs, lacosamide (LCM) and valproate (VPA), in the mouse psychomotor (6 Hz, 32 mA) seizure model.
Material and methods:
In the 6 Hz seizure model, anticonvulsant activity was evaluated in male albino Swiss mice by assessing protection against psychomotor seizures. Dose–response relationships were established using log–probit analysis, and median effective doses (ED50 ± SEM) were calculated. Type I isobolographic analysis was applied to determine the interactions between C-11 and LCM or VPA administered in a fixed-ratio combination (1:1).
Results:
Log–probit analysis demonstrated that C-11, LCM, and VPA administered separately produced clear anticonvulsant effects in the 6 Hz seizure model in mice, and linear regression confirmed parallel dose–response relationships for C-11 in combination with selected ASMs. Type I isobolographic analysis demonstrated that C-11 combined with LCM or VPA (fixedratio of 1:1) produced additive interactions in the 6 Hz model.
Conclusions:
The study shows that mixtures of C-11 with LCM or VPA, evaluated by isobolographic analysis, produce additive interactions in the 6 Hz (32 mA) seizure test in mice. Further studies are required to clarify the mechanisms underlying these effects and to determine their potential clinical relevance.
Currently, polytherapy with two or more antiseizure medications (ASMs) remains one of the therapeutic options for patients with drug-resistant epilepsy. C-11, a pyrrolidine-2,5-dione derivative with previously demonstrated antiseizure activity, has been proposed as a potential adjunct compound. The aim of the present study is to characterize the type of interactions between C-11 and two clinically used ASMs, lacosamide (LCM) and valproate (VPA), in the mouse psychomotor (6 Hz, 32 mA) seizure model.
Material and methods:
In the 6 Hz seizure model, anticonvulsant activity was evaluated in male albino Swiss mice by assessing protection against psychomotor seizures. Dose–response relationships were established using log–probit analysis, and median effective doses (ED50 ± SEM) were calculated. Type I isobolographic analysis was applied to determine the interactions between C-11 and LCM or VPA administered in a fixed-ratio combination (1:1).
Results:
Log–probit analysis demonstrated that C-11, LCM, and VPA administered separately produced clear anticonvulsant effects in the 6 Hz seizure model in mice, and linear regression confirmed parallel dose–response relationships for C-11 in combination with selected ASMs. Type I isobolographic analysis demonstrated that C-11 combined with LCM or VPA (fixedratio of 1:1) produced additive interactions in the 6 Hz model.
Conclusions:
The study shows that mixtures of C-11 with LCM or VPA, evaluated by isobolographic analysis, produce additive interactions in the 6 Hz (32 mA) seizure test in mice. Further studies are required to clarify the mechanisms underlying these effects and to determine their potential clinical relevance.
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| eISSN: | 1898-7516 |
| ISSN: | 1898-2395 |
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