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)

ADD 94057, a metabolite of fluzinamide, manufactured by the A. H. Robins Company, blocks chemically- and electrically-induced seizures in animals. The primary objective of this open add-on study was to evaluate patient tolerability of ADD 94057 at ascending target plasma concentrations. Nine subjects with medically refractory seizures were receiving phenytoin (PHT, 3), carbamazepine (CBZ, 3), or both (3). A pharmacokinetic profile after a single oral 400-mg dose of ADD 94057 was used to calculate ADD 94057 dosages. After a 4-week baseline period, patients were treated for 4 weeks with weekly ADD 94057 dosage escalations. Two patients completed the study at their assigned highest dosage level; the other patients finished the study at lower dosages. The patients receiving PHT (but not CBZ) tolerated higher plasma concentrations of ADD 94057 than did patients receiving CBZ, alone or in combination with PHT. Adverse experiences included headache, ataxia, blurred vision, diplopia, dizziness, lightheadedness, and mild confusion. Eight of nine patients had reductions in seizure frequency from baseline.
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PMID:Pharmacokinetic and dose tolerability study of ADD 94057 in comedicated patients with partial seizures. 173 43

Acute effects of 4 anticonvulsants on hippocampal kindled seizures induced with about 3 Hz electrical stimulations were assessed in cats. The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold, PNT) was used as the indicator for the seizure threshold. Duration of afterdischarge (ADD), ictal and interictal behaviors and serum drug levels were also recorded. PB produced a PNT-increase more prominently than an ADD-decrease with seizure stage regression. PHT produced only a proconvulsive effect by decreasing PNT. CBZ also produced a proconvulsive effect by decreasing PNT at a low dose, and decreased PNT and ADD simultaneously at a high dose. Conversely VPA increased PNT and ADD simultaneously. These results were discussed comparing mainly with a previous study of amygdala-generating seizures.
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PMID:Effects of anticonvulsants on hippocampus-generating seizures. 233 44

The protective activity of carbamazepine (CBZ, 60 min before testing), phenobarbital (PB, 120 min), phenytoin (PHT, 120 min), and valproate (VPA, 30 min) alone or concurrent with methylxanthine derivatives was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were administered intraperitoneally (i.p.), and the protection offered by antiepileptic drugs (AEDs) was expressed as ED50 in mg/kg. Caffeine sodium benzoate in doses of 0.0595-0.476 mmol/kg (11.55-92.4 mg/kg) distinctly reduced the anticonvulsant efficacy of PB, in the highest dose tested with an increase in ED50 value from 19.5 to 38 mg/kg. This methylxanthine derivative in the dose range of 0.119-0.476 mmol/kg (23.1-92.4 mg/kg) also efficiently inhibited the protective action of PHT. When combined with caffeine (0.238 and 0.476 mmol/kg), the ED50 of PHT was raised from 12 to 17 and 24 mg/kg, respectively. In doses of 0.238 and 0.476 mmol/kg, caffeine also diminished the efficacy of CBZ and VPA, and at the highest dose tested the methylxanthine elevated the respective ED50s from 13 to 20.5 mg/kg and from 270 to 420 mg/kg. Generally caffeine sodium benzoate (up to 0.476 mmol/kg) did not affect the plasma levels of studied AEDs, and only at 0.476 mmol/kg did it significantly decrease the level of PHT. Among the other methylxanthines, pentoxifylline (0.238-0.476 mmol/kg; 66.3-132.5 mg/kg) and diprophylline (0.952 mmol/kg; 242.1 mg/kg) inhibited the protective potential of PHT and the respective ED50s were raised from 12 to 16.5, 15.5, and 14 mg/kg. No significant alterations in PHT plasma levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of different methylxanthines on the anticonvulsant action of common antiepileptic drugs in mice. 234 49

The effects of anticonvulsants and Ca2+ channel antagonists on the inositol trisphosphate (IP3) binding and IP3-induced Ca2+ release were examined in brain membrane fractions. Anticonvulsant (PHT and valproate) and Ca2+ channel antagonists (verapamil, diltiazem, flunarizine, nicardipine and cinnarizine), examined did not significantly inhibit the IP3-receptor binding. The Kd and Bmax values of the IP3 binding did not change significantly in the various brain regions of the amygdala-kindled rats, killed 10 days after the last seizure, compared to those of controls. On the other hand, PHT, PB and carbamazepine inhibited the Ca2+ releasing activity of IP3 in the cerebellar membrane fractions by approximately 20% at therapeutic concentrations.
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PMID:Inositol trisphosphate (IP3) receptors and epileptic seizure. 256 Apr 97

We have recently reported some pharmacological studies using a kindling model of epilepsy induced with 1-3 HZ electrical stimulations, referred to as the low-frequency kindling. Since a previous study showed that the effects of psychotropic drugs on limbic seizures were dependent on the location of epileptic focus, we decided to study acute and chronic effects of anticonvulsants on the hippocampus generating seizures to compare with the results of a previous study of the amygdala generating seizures, which was done under the same conditions with this study. The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold) was used as the indicator for the seizure threshold. Duration of after discharge (ADD), ictal and interictal behaviors of the subjected 7 cats, and serum drug levels were also recorded. A dose-dependent increase of serum drug levels was confirmed in each drug, and the values were well comparable with the optimal range in clinical use. In acute experiment PB 5 mg/kg p.o. produced no significant effect on PNT and ADD. PB 10 mg/kg increased PNT significantly (p less than 0.02) at 2 hrs after administration without affecting ADD, but 4 cats presented the seizure-stage regressions. PB 20 mg/kg increased PNT (p less than 0.02) and decreased ADD (p less than 0.02) with the seizure-stage regressions of all the tested cats at 2 hrs after administration, and increased PNT (p less than 0.05) without affecting ADD and seizure stage at 96 hrs after administration. PHT 5, 10, 20 mg/kg decreased PNT (p less than 0.05, 0.02, 0.02, respectively) without affecting ADD at 2 hrs after administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of phenobarbital and phenytoin on hippocampus generating seizures]. 262 37

We report the results of treatment of refractory generalized tonic-clonic status epilepticus in 17 adults. Of 13 patients who received high-dose phenytoin (PHT, mean dose 23.8 mg/kg), seizure control was sustained in five patients. In 12 cases, anesthetic doses of pentobarbital rapidly suppressed convulsions, but sustained control required prolonged treatment. Break-through seizures were, in most cases, explained by inadequate serum pentobarbital concentrations, although we could not establish a therapeutic range of serum concentrations. EEG monitoring is necessary to assess the therapeutic response but is not a reliable index of depth of anesthesia. Some cases developed pharmacodynamic tolerance to pentobarbital. The most serious treatment complications were cardiorespiratory, but the most common and disabling side effects, although reversible, were neurologic. Fifteen patients were discharged from the hospital in stable condition; two patients died, but not as a direct consequence of treatment. Our results suggest a very good outcome of pentobarbital anesthesia for patients in refractory status epilepticus who are a reasonable medical risk and who receive optimal medical management.
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PMID:Treatment of refractory generalized tonic-clonic status epilepticus with pentobarbital anesthesia after high-dose phenytoin. 275 97

The main objective of this study was to determine whether stripentol (STP) alleviates side-effects commonly observed in treated epileptic patients, since preliminary data suggested a positive psychotropic effect. A secondary objective was an evaluation of drug efficacy. Eleven patients with either a drug-resistant epilepsy or toxic effects of AEDs completed the study. Ten had symptomatic partial epilepsies and one an idiopathic generalized epilepsy. STP was added to the baseline therapy (1 or 2 AEDs) and the dose of the baseline AEDs was reduced to maintain plasma levels unchanged (mean reduction: PB 26%, PHT: 49%, CBZ: 38%). Several motor, perceptual and attention tasks and the Washington Psychosocial Seizure Inventory were performed before and after STP administration. Seizure frequency and clinical side-effects were evaluated during a baseline period and after two months of constant therapy. Effects of repeated administration of the neuropsychological battery were assessed by administration of the battery on two occasions at 12-week interval to a randomized subgroup of patients. No practice effect was observed. A trend of improvement (p less than 0.05) in the performance of two tasks requiring sustained attention was noted. Previous side-effects (mainly drowsiness) decreased or disappeared in 7 of 9 patients who became more alert. Six of the nine uncontrolled patients experienced a decrease in seizure frequency equal to or larger than 50 per cent.
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PMID:[Neurophysiological and therapeutic evaluation of stiripentol in epilepsy. Preliminary results]. 336 91

The analysis of clinical features of groups of patients with frequent and rare epileptic seizures showed that the mean age of the first seizure, the mean age at the time of examination, and the mean duration of the disease were not significantly different in both studied groups. In the group with frequent seizures a significantly more frequent presence of features indicating serious organic brain damage was found (more frequent occurrence of known aetiological factors, more cases of posttraumatic epilepsy, psychic and neurological abnormalities). In group C changes in the background activity in EEG were also more frequent. The analysis of pharmacological treatment showed a more frequent application of polytherapy in group C. On the other hand, the mean levels of antiepileptic drugs in the serum and the mean doses of these drugs for kg of body mass were not significantly different in both groups. In about 40% of patients in both groups the prescribed drugs failed to reach the levels generally regarded as therapeutic (slightly more frequently in the group with rare seizures). This was true mainly of PHT since about 81% of patients in both groups failed to reach the therapeutic level of the drug (10 ug/ml). The likely causes of this fact were: too low doses prescribed (55% of the patients were given doses below the generally recommended), lower bioavailability of PHT (27% of patients had no therapeutic level of the drug in the serum, despite doses exceeding 5 mg/kg); or drug interaction. This requires elucidation in further studies.
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PMID:[Characteristics of the clinical features and pharmacological treatment of epileptics with frequent seizures]. 371 70

We examined the effects of conventional antiepileptic drugs (AEDs) on absence-like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded pharmacologically to human absence seizures and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) with both tonic convulsive and absence-like seizures. Cortical and hippocampal EEG activity was recorded with chronically implanted electrodes. The effects of AEDS on seizures of the tremor rat showed profiles similar to those observed in human absence seizures and also in absence-like seizures of SER. The absence-like seizures, associated with paroxysmal bursts of 5-7-Hz spike-wave complexes, were inhibited by trimethadione (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM 100 and 200 mg/kg, i.p.), valproate (VPA 100 mg/kg, i.p.), and phenobarbital (PB 10 and 20 mg/kg, i.p.). Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are consistent with the conclusion that the tremor rat is a useful model for evaluating new AEDS for human absence seizures.
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PMID:Effect of antiepileptic drugs on absence-like seizures in the tremor rat. 764 34

This review summarizes the studies on the cognitive side-effects of two important antiepileptic drugs: phenytoin and carbamazepine. A large literature database was compiled through the DIMDI computer database and the inspection of recent reviews. Only scientific articles published in peer-reviewed journals during the last 25 years were selected. Of the 358 potentially relevant papers on cognitive effects of AEDs, a total of 16 studies have been found that have studied both carbamazepine and phenytoin. After excluding studies with designs that do not permit valid inferences regarding the cognitive effects of AEDs, only five studies remained. The evaluation of these studies reveal that our current knowledge allows us to draw conclusions about the cognitive side-effects of phenytoin and carbamazepine only with great caution. The claim in reviews that 'both drugs have an impact on cognitive function, PHT to a larger degree than CBZ' is simply not supported by valid 'high quality' data. The same is true for the overall conclusion in more recent reviews that 'drug-induced cognitive effects of these AEDs on cognitive function are probably mild or even negligible'. Apparently, the only information that we have is that the differential impact of PHT and CBZ on cognitive function is not extremely different. No conclusive and reconfirmed data are available on the absolute effects of CBZ and PHT (differences between the two drugs and a no-treatment condition). Our review summarizes some recommendations for future studies.
Seizure 1995 Jun
PMID:Phenytoin and carbamazepine: differential effects on cognitive function. 767 Jul 73


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