BIOMAT Database Logo BIOMAT Database Logo

Interactions between zonisamide and conventional antiepileptic drugs in the mouse maximal electroshock test model. 2007

Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland. kinga.borowicz@am.lublin.pl

Despite the major advances in antiepileptic drug (AED) therapeutics, about one third of patients with epilepsy still do not have adequate seizure control with currently available AEDs when prescribed as monotherapy. Typically, in this setting polytherapy with two or more AEDs is used. Zonisamide (ZNS) is a new AED effective in the treatment of refractory epilepsy and since it is only prescribed in polytherapy regimens, its interactions with other AEDs is of particular importance. The aim of this study was to isobolographically determine interactions between ZNS and four conventional AEDs: carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA), in the mouse maximal electroshock (MES)-induced seizure model. The total brain concentrations of conventional AEDs and ZNS were measured with immunofluorescence and high-pressure liquid chromatography (HPLC), respectively, in order to determine any pharmacokinetic contribution in any observed interactions. With isobolography, synergistic interactions were observed for the combination of ZNS plus VPA and ZNS plus PHT at the fixed-ratio of 1:1, while additivity was observed for their combinations at the remaining dose ratios of 1:3 and 3:1. In contrast, the interactions between ZNS and PB and between ZNS and CBZ, applied at the fixed-ratios of 1:3, 1:1 and 3:1 proved to be additive. None of these AED combinations were associated with motor and long-term memory impairment. Furthermore, whilst brain AED concentrations were unaffected by ZNS, PHT significantly increased and PB reduced brain ZNS concentrations. Thus, the resultant interactions between ZNS and PHT and between ZNZ and PB were consequent to both pharmacodynamic and pharmacokinetic components. Finally, one can conclude that because of the synergistic pharmacodynamic interaction between ZNS and VPA, this combination might be useful in clinical practice.

UI MeSH Term Description Entries
D007555 Isoxazoles Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions. Isoxazole
D008297 Male Males
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D004597 Electroshock Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein

Related Publications

Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model.
May 2006, Naunyn-Schmiedeberg's archives of pharmacology,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Interactions between ACE inhibitors and classical antiepileptic drugs in the mouse maximal electroshock seizures.
November 2011, Pharmacology, biochemistry, and behavior,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Isobolographic analysis of interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and four conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model.
January 2009, European journal of pharmacology,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Interactions between non-barbiturate injectable anesthetics and conventional antiepileptic drugs in the maximal electroshock test in mice--an isobolographic analysis.
March 2004, European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Interactions between angiotensin AT1 receptor antagonists and second-generation antiepileptic drugs in the test of maximal electroshock.
June 2014, Fundamental & clinical pharmacology,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Assessment of drug-drug interactions between moxonidine and antiepileptic drugs in the maximal electroshock seizure test in mice.
January 2022, Basic & clinical pharmacology & toxicology,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock seizure model.
January 2010, Pharmacological reports : PR,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Pharmacodynamic and pharmacokinetic characterization of interactions between levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock seizure model: an isobolographic analysis.
January 2006, Epilepsia,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
7-Nitroindazole enhances dose-dependently the anticonvulsant activities of conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model.
January 2006, Pharmacological reports : PR,
Kinga K Borowicz, and Jarogniew J Luszczki, and Grzegorz Sobieszek, and Neville Ratnaraj, and Philip N Patsalos, and Stanisław J Czuczwar
Propafenone enhances the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock model.
June 2016, Pharmacological reports : PR,
Copied contents to your clipboard!