Isobolographic analysis of interactions between remacemide and conventional antiepileptic drugs in the mouse model of maximal electroshock

Borowicz, Kinga K.; Małek, Robert; Łuszczki, Jarogniew J.; Ratnaraj, Neville; Patsalos, Philip N.; Czuczwar, Stanisław J.

doi:10.1016/j.yebeh.2007.04.018

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…, 2003), or determining the dose‐effect site (brain) concentration relationship separate from the pharmacodynamic effect (Luszczki et al. , 2006; Borowicz et al. , 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, there are very few examples establishing the PK ⁄ PD relationship of novel AED in dogs or other preclinical animal models. Much of the previous work that has been conducted was limited to conducting simple regression between area under the plasma concentration-time curve (AUC) and effect, and ⁄ or, assuming a direct link between plasma concentration and effect (Isoherranen et al, 2003), or determining the dose-effect site (brain) concentration relationship separate from the pharmacodynamic effect (Luszczki et al, 2006;Borowicz et al, 2007). Other studies have established a formal PK ⁄ PD relationship, however, the presence or absence of convulsions was converted into a percentage of animals protected (Castel-Branco et al, 2005), which ignores the discrete nature of the data and loses the additional information in a graded clinical score.…”

Section: Discussionmentioning

confidence: 99%

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Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model

Territo¹,

Shannon²,

Newhall³

et al. 2008

Vet Pharm & Therapeutics

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The anticonvulsant ameltolide (LY201116) is a novel potential therapy for the treatment of canine epilepsy. Eight dogs were administered five different oral doses of ameltolide and clinical scoring of the maximal electroshock (MES) induced seizures at 3 and 24 h postdosing were determined in two separate crossover design studies. Plasma ameltolide concentrations were determined at the time of seizures in all dogs and complete plasma concentration-time profiles were also determined in a separate study. A nonlinear mixed effects PK/PD model was fit to the resulting data. A one compartment open model with first order absorption was determined to best fit the ameltolide pharmacokinetics. An effect compartment with a cumulative logistic regression equation was used to establish the PK/PD relationship. The mean bioavailability normalized volume of distribution and the elimination half-life were estimated at 1.20 L/kg and 5.46 h, respectively. The fitted model estimated that from 2 to 15 h following a single 3 mg/kg oral ameltolide dose the mean probability of obtaining a 1 unit reduction in the seizure clinical score severity was greater than 0.80. The utilized PK/PD analysis combined with the canine MES model allowed for the rapid and efficient determination of the plasma ameltolide concentration-anticonvulsant relationship preclinically in dogs.

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“…, 2003), or determining the dose‐effect site (brain) concentration relationship separate from the pharmacodynamic effect (Luszczki et al. , 2006; Borowicz et al. , 2007).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model

Territo¹,

Shannon²,

Newhall³

et al. 2008

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

show abstract

“…Studies also showed that remacemide was significantly less effective than carbamazepine in preventing seizure recurrence. Although significant pharmacodynamic interactions were observed between remacemide and other AEDs (valproate, CBZ, phenytoin, and phenobarbital) (102), unfavorable pharmacokinetic interactions make RMD an unsuitable candidate for adjunctive treatment of epilepsy (103).…”

Section: Dp-valproic Acid (Dp-vpa)mentioning

confidence: 99%

An overview on antiepileptic drugs

2012

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Epilepsy is the most common chronic neurological disorder of the brain. For several decades different kinds of medications have been used to treat epilepsy. Even though many surgical advances has been made and implemented, medications remain the basis of treatment. The search for noble antiepileptic drugs (AEDs) with more selective activity and lower toxicity continues to be an area of intensive investigation in medicinal chemistry. Additionally, drug resistance is an important clinical problem in epilepsy and is associated with an increased risk of morbidity and mortality. This review intends to present a comprehensive overview on AED in particular along with discussion on some aspects of associated drug resistance and combination therapy.

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Nano-Hydrogel for the Treatment of Depression and Epilepsy

Yang

2022

j biomed nanotechnol

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This article first combines nano-carrier technology, the electrophysiological mechanism of seizures, and brain targeting technology to prepare new nano-hydrogels. Secondly, through the discharge information generated during the seizure and the electric field responsiveness of the nano-hydrogel, the free drug concentration in the brain area related to the seizure is increased, thereby, limiting the abnormal discharge of the focus to the local area and suppressing it in time. Finally, this article examines the impact of nano-hydrogel on the epilepsy and depression using relevant studies. The experimental observations revealed that the yield of the nano-hydrogel synthesized after 24 h of sapon-free emulsion polymerization was 50 to 70%, the swelling rate was 400 to 1700%, and the viscosity of the 20 mg/mL nano-hydrogel dispersion was 3.9 to 17.0 mPa· s. Furthermore, because the total efficiency was 0.952, the nano-hydrogels have a reduced recurrence rate and a better effect on the depression improvement.

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Isobolographic analysis of interactions between remacemide and conventional antiepileptic drugs in the mouse model of maximal electroshock

Cited by 3 publications

References 36 publications

Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model

Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model

An overview on antiepileptic drugs

Nano-Hydrogel for the Treatment of Depression and Epilepsy

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