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Antiepileptic Effect (antiepileptic + effect)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Antiepileptic Effect of Gap-junction Blockers in a Rat Model of Refractory Focal Cortical Epilepsy

EPILEPSIA, Issue 7 2006
Karen E. Nilsen
Summary:,Purpose: Epilepsy is the most common serious neurologic disease, and current treatments are ineffective for ,30% of patients. Gap junctions have been implicated in seizure generation and propagation, and as such, may represent a novel therapeutic target but have been little investigated in vivo. We set out to assess the efficacy and tolerability of gap-junction blockers delivered to the seizure focus in a well-characterized model of refractory cortical epilepsy in rats. Methods: A chronic epilepsy focus was induced in the cortex of rats by using tetanus toxin, and subsequent studies were conducted in freely moving unanesthetized animals with frequent spontaneous seizures, as we previously described. Carbenoxolone, meclofenamic acid, and saline were applied directly to the seizure focus. EEG, electromyogram (EMG), and behavioral parameters were measured for ,1 h before drug infusion and for ,3 h afterward. No ill effects were observed. Results: An immediate and marked reduction in percentage of seizure time was seen in rats receiving carbenoxolone (baseline, 69.4%± 7.0% (SEM); maximum effect, 9.3%± 3.5%, p ,0.001) and meclofenamic acid (baseline, 58.3%± 3.7%; maximum effect, 0.92%± 0.92%, p < 0.001). No effect was seen after saline infusion. Conclusions: Gap-junction blockers applied focally are effective at suppressing seizures and, as such, represent a potential new treatment for epilepsy. Development of focal treatment strategies is essential in this regard. [source]

Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures

EPILEPSIA, Issue 9 2010
Annelies Van Dycke
Summary Purpose:, Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug-related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods:, Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 ,l/h) (treatment). In 7 of 10 adenosine-treated rats, saline was also delivered during a washout period. Results:, During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine-treated rats (p < 0.01). Four rats had a seizure frequency reduction of at least 50%. Both nonconvulsive and convulsive seizures significantly decreased during the treatment period. In the saline-control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions:, This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures. [source]

Experimental and Clinical Evidence for Loss of Effect (Tolerance) during Prolonged Treatment with Antiepileptic Drugs

EPILEPSIA, Issue 8 2006
Wolfgang Löscher
Summary:, Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most first-generation AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of an AED may be an important reason for failure of drug treatment. Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists. [source]

Three cases of PICU sedation with isoflurane delivered by the ,AnaConDa®'

PEDIATRIC ANESTHESIA, Issue 10 2005
PETER V. SACKEY MD
Summary Prolonged sedation in the pediatric intensive care unit may be difficult because of tolerance, drug dependence and withdrawal, drug interactions and unwanted drug effects. We present three patients sedated with isoflurane via the Anesthetic Conserving Device, AnaConDa®. AnaConDa® is a modified heat and moisture exchanger that allows evaporation and delivery of inhalational anesthetics without an anesthesia machine, vaporizer or adapted ventilator. Two patients with abdominal complications and prolonged sedation for mechanical ventilation were converted to isoflurane sedation for several days. The third patient with refractory status epilepticus received isoflurane to treat epileptiform electroencephalogram activity. Patients weighing 40 and 30 kg were treated with AnaConDa® placed at the Y-piece, while the patient weighing 20 kg was treated with AnaConDa® in the inspiratory limb of the respiratory circuit. Adequate sedation was achieved with endtidal isoflurane concentration of 0.3,0.4%, while antiepileptic effect was achieved at a higher dose, 0.9%. Intravenous sedatives could be reduced or discontinued during isoflurane sedation. Inhaled sedation of isoflurane with AnaConDa® was effective in these patients. It may provide an alternative in difficult cases needing prolonged sedation and should be evaluated further. [source]