Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0036572 (
seizures
)
80,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It is believed that some pitfalls in the treatment of epilepsy such as serious side effects of medications and drug resistance may be resolved by natural compounds. Auraptene belongs to coumarins and is found in citrus peel. We hypothesized that auraptene might have anticonvulsant properties. Kindling was induced by repeated intraperitoneal (IP) injections of pentylenetetrazol (PTZ, 35 mg/kg) with two-day intervals for 24 days in male albino mice. Three groups received IP injections of auraptene (12.5, 25, and 50 mg/kg). Three control groups received vehicle, diazepam (3 mg/kg, IP), and vitamin E (150 mg/kg, IP).
Seizure
-related behaviors were recorded for 30 min after PTZ injection. Moreover, malondialdehyde and reduced glutathione (GSH) were measured in the brain. The results indicated that auraptene at the dose of 12.5 mg/kg and vitamin E significantly prolonged the latency to stage 2 of
seizures
(
P
< 0.01). Auraptene at the doses of 25 mg/kg and 50 mg/kg, prolonged the latency to stage 4 (
P
< 0.01) and reduced stage 5 duration of
seizures
(
P
< 0.01). All doses of auraptene reduced median of
seizure
scores (
P
< 0.01). The kindled control group had
MDA
levels similar to intact animals but had a lower concentration of GSH (
P
< 0.001). None of the tested compounds changed the malondialdehyde concentration significantly. However, auraptene at the dose of 50 mg/kg and vitamin E increased GSH levels (
P
< 0.05). The results suggest that auraptene had anticonvulsant effects in PTZ-induced chemical kindling that was mediated by mechanisms other than the antioxidant effect of auraptene.
...
PMID:The Protective Effect of Auraptene Against Oxidative Stress and Pentylenetetrazol-Induced Chemical Kindling in Mice. 3264 49
Eslicarbazepine acetate (ESL) is a dibenzazepine anticonvulsant approved as adjunctive treatment for partial-onset epileptic
seizures
. Following first pass hydrolysis of ESL, S-licarbazepine (S-Lic) represents around 95% of circulating active metabolites. S-Lic is the main enantiomer responsible for anticonvulsant activity and this is proposed to be through the blockade of voltage-gated Na
+
channels (VGSCs). ESL and S-Lic both have a voltage-dependent inhibitory effect on the Na
+
current in N1E-115 neuroblastoma cells expressing neuronal VGSC subtypes including Na
v
1.1, Na
v
1.2, Na
v
1.3, Na
v
1.6, and Na
v
1.7. ESL has not been associated with cardiotoxicity in healthy volunteers, although a prolongation of the electrocardiographic PR interval has been observed, suggesting that ESL may also inhibit cardiac Na
v
1.5 isoform. However, this has not previously been studied. Here, we investigated the electrophysiological effects of ESL and S-Lic on Na
v
1.5 using whole-cell patch clamp recording. We interrogated two model systems: (1)
MDA
-MB-231 metastatic breast carcinoma cells, which endogenously express the "neonatal" Na
v
1.5 splice variant, and (2) HEK-293 cells stably over-expressing the "adult" Na
v
1.5 splice variant. We show that both ESL and S-Lic inhibit transient and persistent Na
+
current, hyperpolarise the voltage-dependence of fast inactivation, and slow the recovery from channel inactivation. These findings highlight, for the first time, the potent inhibitory effects of ESL and S-Lic on the Na
v
1.5 isoform, suggesting a possible explanation for the prolonged PR interval observed in patients on ESL treatment. Given that numerous cancer cells have also been shown to express Na
v
1.5, and that VGSCs potentiate invasion and metastasis, this study also paves the way for future investigations into ESL and S-Lic as potential invasion inhibitors.
...
PMID:Inhibitory Effect of Eslicarbazepine Acetate and S-Licarbazepine on Na
v
1.5 Channels. 3312 7
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