RESEARCH PAPER
Isobolographic characterization of interaction of levetiracetam with clobazam in the mouse 6 Hz psychomotor seizure model
| 1 | Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland; Department of Pathophysiology, Medical University, Lublin, Poland |
| 2 | Department of Pathophysiology, Medical University, Lublin, Poland |
| 3 | Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland |
| 4 | Department of Public Health, Institute of Rural Health, Lublin, Poland |
CORRESPONDING AUTHOR
Jarogniew J. Łuszczki
Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland.
Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland.
J Pre Clin Clin Res. 2012;6(1):25–30
KEYWORDS
ABSTRACT
Introduction and objective:
The aim of this study was to characterize the anticonvulsant effects of levetiracetam (LEV) in combination with clobazam (CLB – a second-generation antiepileptic drug), in the mouse 6 Hz psychomotor seizure model.
Material and Methods:
Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to characterize the consequent anticonvulsant interactions between the drug combinations. Potential concurrent adverse-effect profiles of interactions between LEV and CLB were evaluated in the chimney (motor performance), passive-avoidance (long-term memory), and grip-strength (muscular strength) tests.
Results:
LEV administered singly was associated with a DRRC that was parallel to that for CLB. With isobolography for parallel DRRCs, the combination of LEV with CLB at three fixed-ratios of 1:3, 1:1 and 3:1 exerted additive interaction. None of the combinations were associated with any concurrent adverse effects with regards to motor coordination, long-term memory or muscular strength.
Conclusions:
LEV combined with CLB exerted additive interaction in the mouse 6 Hz psychomotor seizure model.
The aim of this study was to characterize the anticonvulsant effects of levetiracetam (LEV) in combination with clobazam (CLB – a second-generation antiepileptic drug), in the mouse 6 Hz psychomotor seizure model.
Material and Methods:
Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Isobolographic analysis for parallel dose-response relationship curves (DRRCs) was used to characterize the consequent anticonvulsant interactions between the drug combinations. Potential concurrent adverse-effect profiles of interactions between LEV and CLB were evaluated in the chimney (motor performance), passive-avoidance (long-term memory), and grip-strength (muscular strength) tests.
Results:
LEV administered singly was associated with a DRRC that was parallel to that for CLB. With isobolography for parallel DRRCs, the combination of LEV with CLB at three fixed-ratios of 1:3, 1:1 and 3:1 exerted additive interaction. None of the combinations were associated with any concurrent adverse effects with regards to motor coordination, long-term memory or muscular strength.
Conclusions:
LEV combined with CLB exerted additive interaction in the mouse 6 Hz psychomotor seizure model.
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