Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nimodipine, a calcium channel blocker with high affinity for central dihydropyridine Ca2+ channels, produced a dose-dependent suppression of electrically induced seizures in the rabbit. Verapamil, a diphenylalkylamine which acts at peripheral Ca2+ channels, was ineffective. Phenytoin was less effective than nimodipine. These results suggest that calcium flux into neurons may be a biochemical precipitant for seizure genesis. Centrally acting calcium channel blockers may prove to be a new class of anticonvulsants.
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PMID:Inhibition of electrically induced seizures by a dihydropyridine calcium channel blocker. 243 42

Recently, a theoretical scheme offered mechanisms by which phenytoin exerts its antiepileptic effects. Two predictions arising from this proposal are that phenytoin would suppress alterations in the potency of excitatory neurotransmission engendered by repetitive neural activation and that this effect would be augmented by displacing the extracellular concentration of K+ ([K+]0) away from its normal resting level. In the present study, we tested these predictions by examining the effects of phenytoin on short- and long-term functional plasticity in vitro in the hippocampus. Extracellular field potentials were recorded in the CA1 region of the rat hippocampal slice in response to stimulation of the Schaeffer collaterals. Phenytoin (20 micrograms/ml) did not affect baseline excitatory neurotransmission as measured by input-output curves (population spike amplitude versus stimulus intensity) obtained at low stimulus rates. The drug also had no effect on either frequency potentiation (2.5 Hz) or long-term potentiation (50 Hz, 500 msec; or 400 Hz, 20 msec). When [K+]0 was raised to levels seen during seizures, the drug still did not alter frequency potentiation or long-term potentiation induced by either type of stimulus train. Phenytoin also had no effect on either stimulus-locked or spontaneous epileptiform bursts that appear in conjunction with elevated [K+]0 or on stimulus-locked bursts that appear in the presence of 0.75 mM extracellular calcium. These results, showing that certain forms of functional synaptic plasticity are not affected by phenytoin, suggest a means by which phenytoin could exert its antiepileptic action without interfering with normal brain function.
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PMID:Phenytoin does not block hippocampal long-term potentiation or frequency potentiation. 245 69

Phenytoin absorption is reportedly significantly altered in the presence of continuously administered enteral feedings, resulting in subtherapeutic serum phenytoin concentrations and loss of seizure control. We administered 500 mg of phenytoin as the suspension to five volunteers who were not receiving enteral feeding, again while they ingested protein hydrolysate enteral feedings hourly, and again during hourly ingestions of meat-base enteral feeding. Serum phenytoin concentrations, measured 3, 6, 9, 12, and 24 hours after phenytoin ingestion, were lowest with protein hydrolysate feedings. Mean serum phenytoin concentrations were consistently higher with the meat-base feeding than with the protein hydrolysate formula, although levels did not reach those of the control period. These data are in keeping with our previous observation that it is easier to attain therapeutic serum phenytoin concentrations in patients receiving a meat-base enteral feeding than in those receiving a protein hydrolysate formula.
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PMID:Phenytoin absorption in volunteers receiving selected enteral feedings. 250 37

Alterations of consciousness with impaired perception and drive persisting over hours to days can be due to a nonconvulsive status epilepticus. This possibility has to be considered not only in patients with already known epilepsy, but also in those with a negative history for seizure disorders. The immediately recorded electroencephalogram (EEG) provides decisive clues. In the case of petit mal status most frequently appear tiredness, reduced vigilance and lack of drive. The EEG shows a generalized spike-wave activity. In status psychomotoricus, the clinical symptomatology varies from case to case. It can be characterized by anxiety, dreamy states or productive-psychotic states with agitation, automatisms and hallucinations. In the EEG a temporal or temporally-accentuated epileptic activity will be recorded. Transitional and mixed forms of petit mal status and status psychomotoricus can also be found. I.v. injections of benzodiazepines (clonazepam, diazepam) are an appropriate therapy for any type of nonconvulsive status epilepticus. Phenytoin is indicated in status psychomotoricus, but contra-indicated in the case of petit mal status.
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PMID:[Epileptic impaired consciousness in adults]. 250 9

Repeated administration of the beta-carboline FG 7142 results in sensitisation to its convulsant effects (chemical kindling); acutely FG 7142 is not convulsant, but following several treatments full seizures develop. It has been suggested that the increased sensitivity results from changes in benzodiazepine (BZ)/GABA receptor function. The present experiments studied the ability of BZ receptor ligands and anticonvulsant drugs with diverse mechanisms of action to block the expression and development of kindling to once daily injection of FG 7142 (40 mg/kg, i.p.) in mice. In fully kindled mice, the BZ receptor agonists clonazepam, ZK 93,423 and CL 218,872, and the antagonists flumazenil and ZK 93,426 prevented FG 7142 convulsions, as did 2 anticonvulsants, sodium valproate, possibly acting by influencing GABAergic transmission, and ethosuximide. A further two substances, MK 801 and 2-chloradenosine which act respectively via glutamatergic and purinergic mechanisms were also effective. When administered concomitantly with repeated FG 7142, all of these substances prevented or strongly reduced the development of kindling. Phenytoin and carbamazepine were ineffective in protecting against FG 7142 convulsions in kindled mice, and in preventing the development of kindling when administered repeatedly together with FG 7142. Since MK 801 and 2-chloradenosine prevented kindling, these results suggest that an interaction of FG 7142 with BZ receptors is not sufficient to induce kindling, which may instead result from secondary changes in sites distant from BZ/GABA receptors.
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PMID:Blockade of FG 7142 kindling by anticonvulsants acting at sites distant from the benzodiazepine receptor. 254 58

Antiepileptic drugs (AEDs) vary in their efficacy against generalized tonic-clonic, myoclonic, and absence seizures, suggesting different mechanisms of action. Phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) reduced the ability of mouse central neurons to sustain high-frequency repetitive firing of action potentials (SRF) at therapeutic free serum concentrations. Phenobarbital (PB) and the benzodiazepines (BZDs), diazepam (DZP), clonazepam (CZP), and lorazepam (LZP), also reduced SRF, but only at supratherapeutic free serum concentrations achieved in treatment of generalized tonic-clonic status epilepticus. These AEDs interact with sodium channels to slow the rate of recovery of the channels from inactivation. The BZDs and PB enhanced gamma-aminobutyric acid (GABA) responses evoked on mouse central neurons by binding to two different sites on the GABAA receptor channel. BZDs increased the frequency of GABA receptor channel openings. In contrast, barbiturates increased the open duration of these channels. VPA enhanced brain GABA concentration and may enhance release of GABA from nerve terminals. Ethosuximide (ESM) reduced a small transient calcium current which has been shown to be involved in slow rhythmic firing of certain neurons. Reduction of SRF, enhancement of GABA-ergic inhibition, and reduction of calcium current may be, in part, the bases for AED action against generalized tonic-clonic, myoclonic, and absence seizures, respectively.
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PMID:Antiepileptic drug actions. 255 Feb 16

In North America, magnesium sulfate is the traditional treatment for severe preeclampsia and eclampsia. Its use has been strongly criticized, in that it acts peripherally with no central effect and maternal and neonatal complications are well known. Phenytoin, the mechanism of action of which is clear, seems a logical alternative. Our aim was to develop a safe, practical, effective regimen with the use of phenytoin. In this prospective, descriptive study four dosage regimens were investigated in 104 patients. The initial regimens produced unexpected and unacceptable side effects in comparison with the nonpregnant population. The final regimen (15 mg/kg intravenously, given as 10 mg/kg initially then 5 mg/kg 2 hours later) provided therapeutic levels and had minimal maternal and perinatal side effects. No seizures occurred after its correct usage. This regimen is simple, safe, effective, and provides ongoing anticonvulsant coverage in the postpartum period. We suggest that phenytoin may represent a suitable alternative anticonvulsant in this condition.
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PMID:Clinical experience with phenytoin prophylaxis in severe preeclampsia. 240 35

Phenytoin (DPH) was delivered to the brain by a dihydropyridine in equilibrium pyridinium salt redox system, which was evaluated for anticonvulsant activity. Following iv injection of the lipophilic delivery system of DPH (2) to rats, concentrations of DPH were lower but sustained and, after 30 min, essentially the same as the levels after equimolar administration of DPH. While 2 delivered the same levels of DPH to the brain as DPH did, it was twice as potent as DPH in rats (ED50 was 7.5 mumol/kg for 2 and 14.2 mumol/kg for DPH) and mice (2: 10.5; DPH: 23.9) against maximal electroshock seizures (MES), and seven times more potent in mice (2: 10.0, DPH: 70.6) against maximal pentylenetetrazole seizures (MPS). Moreover, 2 was active against pentylenetetrazole threshold seizures (PTS) in mice and rats (ED50 = 44.1 and 40.5 mumol/kg, respectively), while DPH was ineffective (up to a dose of 79.2 mumol/kg). After evaluation of acute neurological toxicity in rats, 2 was found to possess 1.5 times higher a protective index (for MES) than DPH. It appeared also that while DPH was 2.9 times less sensitive to MPS than to MES, 2 was equally potent to both types of convulsions. Thus, the data indicate that 2 delivered DPH more efficiently to the brain. The better anticonvulsant activity (quantitatively as well as qualitatively) of 2 can be explained on the basis of an improved distribution in the brain due to its higher lipophilicity, and by favorable regional differences in the rates of conversion of 2 to DPH at the convulsing foci.
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PMID:Improved anticonvulsant activity of phenytoin by a redox brain delivery system. III: Brain uptake and pharmacological effects. 260 Jul 90

The anticonvulsive action of vanillin, an antiepileptic agent structurally related to vanillyl alcohol isolated from Gastrodia elata Blume, on the fully amygdala-kindled seizures was investigated. Fully kindled seizures were produced by repeated application of low intensity electrical stimulation to the basolateral amygdala once per day. Fifteen consecutive stimulations were needed to reach the first stage 5 seizures at which animals showed behavioral convulsions and electroencephalographic abnormalities. The stage 5 seizures were suppressed by vanillin ip 1 h before stimulation with the ED50 of 286 mg/kg. Meanwhile, the epileptic afterdischarge duration was significantly shortened. Phenytoin at a nontoxic dose 50 mg/kg ip obviously reduced the stage 5 seizures. The present study provides a very useful experimental model of chronic epilepsy to detect anticonvulsants.
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PMID:[The effect of vanillin on the fully amygdala-kindled seizures in the rat]. 261 88

Phenytoin (15 mg/kg) was administered intravenously to 189 patients shortly before their intracranial, supratentorial surgery was completed. Intravenous phenytoin of 5-6 mg/kg/day in three divided doses was administered daily for the first 3 postoperative days. Therapeutic serum levels (10-20 micrograms/mL) were achieved in 113 (59.8%) patients. An equally constituted, randomized control group of 185 patients received a placebo under identical conditions. The group receiving phenytoin had only one immediate and two early postoperative seizures. The 185 controls had four immediate and nine early postoperative seizures. None of the follow-up computed tomography scans of the patients with seizures showed postoperative hematoma. One patient had a significant tension pneumocranium, a possible cause of postoperative seizures. To avoid a decrease in the serum anticonvulsant level due to intraoperative blood loss, it is suggested that for patients who need an urgent or emergent craniotomy, prophylatic anticonvulsant medication should be given at least 20 minutes before completion of wound closure.
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PMID:Prophylactic anticonvulsants for prevention of immediate and early postcraniotomy seizures. 271 9


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