Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of various calcium channel inhibitors have been studied in lithium-pilocarpine model of status epilepticus. Status epilepticus was induced by administration of lithium chloride (3 meq/kg) followed 21 hr later by pilocarpine (30 mg/kg). Diltiazem (5 and 10 mg/kg) was not effective in delaying onset of convulsions. Verapamil (20 mg/kg) showed protection against lithium-pilocarpine-induced convulsions. The dihydropyridine nifidepine (2.5 and 5 mg/kg) did not show any protection in this model. Amlodipine (5 and 10 mg/kg) as partially protective. Flunarizine (10 and 20 mg/kg) delayed the onset of forelimb clonus and rearing and only 60% of the rats underwent status in the 20 mg/kg group. Pre-treatment of MK-801 led to a potentiation of the antiseizure activity of calcium channel inhibitors. The percent increase in amplitude at various time points with amlodipine pretreatment was significant only at the 30th min recording, and at the rest of the time frames was practically similar as the controls. It can be concluded that the anticonvulsant action of MK-801 can be enhanced by centrally acting calcium channel inhibitors.
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PMID:Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers. 1121 25

We report on the use of the voltage-gated calcium channel blocker (Vg-CCB), verapamil, as an add-on anticonvulsant medication in two girls, 4 and 14 years of age, who were affected by severe myoclonic epilepsy in infancy (SMEI) or Dravet syndrome, a channelopathy caused by abnormalities in the voltage-gated sodium channel neuronal type alpha1 subunit (SCN1A) gene at 2q24. Both girls had pharmacoresistant epilepsy and developmental delay. Mutation analysis for the SCN1A gene revealed a missense mutation in exon 2 in the 4-year-old girl. Verapamil was co-administered in both children with a prompt response in controlling status epilepticus, myoclonic jerks, and partial and generalized seizures. The therapeutic effect lasted 13 months in the 14-year-old girl, while it is still present after a 20-month follow-up period in the 4-year-old girl who, in addition, has experienced improvement in motor and language development. The verapamil vVg-CCB, which crosses the blood-brain barrier (BBB): (a) inhibits the P-glycoprotein, an active efflux transporter protein expressed in normal tissue, including the brain, which is believed to contribute to the in situ phenomenon of multidrug resistance; and (b) may regulate membrane depolarization induced by abnormal sodium channels functions by modulating the abnormal Ca++ influxes into neurons with subsequent cell resting. This is the first report on long-lasting verapamil therapy in SMEI. The functional consequences of such in vivo modulating effects on Ca++ channels could contribute to rational targeting for future molecular therapeutic approaches in pharmacoresistant epileptic channelopathies.
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PMID:Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy. 1948 7

Almost one-third of the people suffering from epilepsy continue to have seizures in spite of using appropriate antiepileptics. Pharmacoresistance is defined as the failure to achieve seizure control with two or more anticonvulsant medications at appropriate daily dosage. Here, we discuss one such gentleman whose seizures had been intractable despite multiple antiepileptic drugs in maximum tolerable doses. Verapamil, a calcium channel blocker, was used for its P-glycoprotein inhibition properties to overcome the pharmacoresistance in this patient with satisfactory seizure control. There are a few studies with limited patients on the successful usage of verapamil in a patient with pharmacoresistant status epilepticus (SE). We intend to publish this case report to draw interest among the critical care physicians on pharmacoresistant SE, the different hypotheses that prevail, its causes and the available management strategies.
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PMID:Verapamil as an Adjuvant Treatment for Drug-Resistant Epilepsy. 3029 38