Polygonogram and isobolographic analysis of interactions between various novel antiepileptic drugs in the 6-Hz corneal stimulation-induced seizure model in mice

Autor: Hubert Bojar, Mirosław Zagaja, Sławomir Karwan, Magdalena Florek-Łuszczki, Zbigniew Plewa, Anna Panasiuk, Jarogniew J. Luszczki
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Levetiracetam
Lacosamide
medicine.medical_treatment
Pregabalin
Stimulation
Pharmacology
Cornea
Mice
chemistry.chemical_compound
Epilepsy
0302 clinical medicine
Medicine and Health Sciences
Drug Interactions
Electroshock
Multidisciplinary
Pharmaceutics
Retigabine
Drugs
Drug Synergism
Neurology
Medicine
Anticonvulsants
Drug Therapy
Combination
Gabapentin
Anatomy
Research Article
medicine.drug
Drug Administration
Science
Ocular Anatomy
Drug-Drug Interactions
03 medical and health sciences
Drug Therapy
Adverse Reactions
Seizures
Ocular System
medicine
Animals
Muscle Strength
Drug Screening
business.industry
Biology and Life Sciences
equipment and supplies
medicine.disease
Disease Models
Animal
030104 developmental biology
Anticonvulsant
chemistry
sense organs
business
030217 neurology & neurosurgery
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 6, p e0234070 (2020)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0234070
Popis: Pharmacotherapy with two antiepileptic drugs in combination is usually prescribed to epilepsy patients with refractory seizures. The choice of antiepileptic drugs in combination should be based on synergistic cooperation of the drugs with respect to suppression of seizures. The selection of synergistic interactions between antiepileptic drugs is challenging issue for physicians, especially, if 25 antiepileptic drugs are currently available and approved to treat epilepsy patients. The aim of this study was to determine all possible interactions among 5 second-generation antiepileptic drugs (gabapentin (GBP), lacosamide (LCM), levetiracetam (LEV), pregabalin (PGB) and retigabine (RTG)) in the 6-Hz corneal stimulation-induced seizure model in adult male albino Swiss mice. The anticonvulsant effects of 10 various two-drug combinations of antiepileptic drugs were evaluated with type I isobolographic analysis associated with graphical presentation of polygonogram to visualize the types of interactions. Isobolographic analysis revealed that 7 two-drug combinations of LEV+RTG, LEV+LCM, GBP+RTG, PGB+LEV, GBP+LEV, PGB+RTG, PGB+LCM were synergistic in the 6-Hz corneal stimulation-induced seizure model in mice. The additive interaction was observed for the combinations of GBP+LCM, GBP+PGB, and RTG+LCM in this seizure model in mice. The most beneficial combination, offering the highest level of synergistic suppression of seizures in mice was that of LEV+RTG, whereas the most additive combination that protected the animals from seizures was that reporting additivity for RTG+LCM. The strength of interaction for two-drug combinations can be arranged from the synergistic to the additive, as follows: LEV+RTG > LEV+LCM > GBP+RTG > PGB+LEV > GBP+LEV > PGB+RTG > PGB+LCM > GBP+LCM > GBP+PGB > RTG+LCM.
Databáze: OpenAIRE
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