کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5628594 1579890 2017 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ivabradine attenuates the anticonvulsant potency of lamotrigine, but not that of lacosamide, pregabalin and topiramate in the tonic-clonic seizure model in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Ivabradine attenuates the anticonvulsant potency of lamotrigine, but not that of lacosamide, pregabalin and topiramate in the tonic-clonic seizure model in mice
چکیده انگلیسی


- Ivabradine attenuates the antiseizure action of LTG in the MES test in mice.
- Ivabradine has no impact on the antiseizure action of LCM, PGB and TPM.
- Interactions between ivabradine and tested AEDs are pharmacodynamics in nature.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are involved not only in synaptic transmission and neuronal excitability under physiological conditions, but also in seizure activity. To determine the influence of ivabradine (an HCN channel inhibitor) on the anticonvulsant potency of four novel antiepileptic drugs (AEDs: lacosamide, lamotrigine, pregabalin and topiramate) in the mouse maximal electroshock-induced seizure (MES) model. Adult male albino Swiss mice were challenged with maximal electroconvulsions (electric current of 25 mA delivered via auricular electrodes). Total brain concentrations of AEDs were measured with high-pressure liquid chromatography. Ivabradine (10 mg/kg, i.p.) significantly reduced the anticonvulsant potency of lamotrigine by elevating the ED50 value of the AED from 7.48 (6.15-9.11) to 10.07 (8.85-11.45) mg/kg (P < 0.05) in the mouse MES model. In contrast, ivabradine (10 mg/kg, i.p.) did not significantly affect the anticonvulsant potency of lacosamide, pregabalin or topiramate in the mouse MES model. Additionally, ivabradine had no impact on total brain concentrations of all the studied AEDs in mice. A special caution is advised when combining ivabradine with lamotrigine in epilepsy patients due to the possible pharmacodynamic reduction of the anticonvulsant action of the later drug. The combinations of ivabradine with lacosamide, pregabalin and topiramate seem to be pharmacodynamic and neutral from a preclinical viewpoint.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Epilepsy Research - Volume 133, July 2017, Pages 67-70
نویسندگان
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