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)

Kainic acid (KA 4-14 mg/kg) administered intraperitoneally (i.p.) produces automatisms (scratching until third postnatal week, "wet dog" shakes thereafter), and clonic and tonic-clonic seizures in rats aged 7, 12, 18, 25, and 90 days. Administration of carbamazepine (CBZ) i.p. (25 or 50 mg/kg), phenobarbital (PB 20-80 mg/kg), clonazepam (CZP 0.2 or 1 mg/kg), or valproate (VPA 200 mg/kg) influenced neither incidence nor latency of automatisms. Clonic seizures that are regularly observed after the third postnatal week in controls were either abolished or substantially suppressed by any of the aforementioned antiepileptic drugs (AEDs). Tonic-clonic seizures observed in the first 3 postnatal weeks were suppressed only by solvent [including propyleneglycol (PEG), ethanol, and water]; the effect of AEDs on tonic-clonic seizures was proconvulsant instead. The automatisms were most resistant to AED therapy. These results induce some doubts about the adequacy of the KA model for identifying AEDs effective against complex partial seizures, but forthcoming AEDs that suppress automatisms in the KA rat model might also be active against human complex partial seizures.
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PMID:Action of antiepileptic drugs against kainic acid-induced seizures and automatisms during ontogenesis in rats. 146 81

1) CZP had marked effects on RD. RD disappeared in 8 (73%) of 11 patients treated with CZP alone and 6 (43%) of 14 treated with CZP in combination with other drugs. Even when RD persisted, its amplitude and frequency decreased in some patients. 2) In the group treated with CZP in combination with other drugs, RD disappeared in all 5 patients with the persistent RD, of whom 2 had arachnoid cyst. Of the 6 patients with frequent seizures, 2 were subsequently diagnosed as having CPS and SPS, respectively. Patients who did not respond to CPZ included those in whom the diagnosis of BECCT should be reconfirmed, and electro-clinical response may be also useful for diagnosing RD. 3) In patients treated with CZP alone for a short-term treatment of BECCT, the drug administration could be discontinued only in one. A longer follow-up study is necessary to reach a conclusion in future.
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PMID:The effects of clonazepam on rolandic discharge of benign epilepsy of children with centro-temporal EEG foci. 176 50

We reported a case of early infantile epileptic encephalopathy (EIEE) due to perinatal hypoxic-ischemic brain damage. This infant had frequent brief tonic seizures in series accompanied by apnea and bradycardia since two days after birth. Her EEG showed a typical suppression burst pattern. We administered PB. VPA and CZP, but could not control her seizures at all. Then, a thyrotropin releasing hormone (TRH) analog, in addition to PB and VPA, was administered intravenously (0.5 mg/day) to her. Three weeks after the administration of this TRH analog, her seizures ceased completely. We suggest that TRH analog therapy should be considered as one of therapeutics for EIEE whose prognosis is expected to be poor.
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PMID:[Effectiveness of TRH analog in a case of early infantile epileptic encephalopathy]. 212 Nov 73

The anticonvulsant effects of two doses of clonazepam (CZP, Rivotril Roche, 0.1 and 1 mg/kg i.p.) were studied on model motor seizures induced by strychnine, bicuculline, 3-mercaptopropionic acid and metrazol in male laboratory rats (Wistar strain). In the first part the effects of different doses of the convulsants were investigated and for interaction with CZP doses were chosen after which more than 70% of the animals displayed generalized tonic-clonic convulsions (a grand mal seizure). Strychnine induced this type of seizure only: two doses (2 and 3 mg/kg s.c.) were used. CZP reduced the incidence of convulsions only after the larger dose, but plain solvent (propylene glycol, ethanol, water) was equally effective. The other substances first induced a seizure of minimal (mainly clonic) convulsions and only later a grand mal seizure. CZP was highly effective against bicuculline (3 mg/kg s.c.) and metrazol (100 mg/kg s.c.), but was less so against 3-mercaptopropionic acid. The effect on grand mal seizures was more pronounced in every case than on minimal seizures. The decisive role in the anticonvulsant effect of CZP is played by the mechanisms by which the convulsants induce epileptic manifestations. CZP is most effective against substances acting on the supramolecular complex GABA receptor (benzodiazepine receptor) chloride ionophore (bicuculline and probably metrazol).
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PMID:Anticonvulsant effects of clonazepam on chemically induced convulsions. 215 Sep 91

The influence of clonazepam on thalamo-cortical phenomena was studied in acute experiments in 20 rats. Early components of cortical responses to electrical stimulation of either LA or VDM thalamic nuclei remained unchanged. Only the latency of the late N2 component was significantly shortened after CZP. CZP did not change the incidence of rhythmic after-discharge ("thalamo-cortical spindles") and tended to prolong them. Two types of self-sustained after-discharges of an epileptic nature which could appear after the end of rhythmic thalamic stimulation were influenced differently: Spike-and-wave type was invariably suppressed, serrated wave type of SSAD was generally unchanged by CZP. This last finding speaks in favour of the hypothesis that these two types of SSADs could serve as models of two different epileptic seizures.
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PMID:Influence of clonazepam on thalamocortical phenomena in rats. 685 98

A novel anticonvulsant benzodiazepine bretazenil (Ro 16-6028) was studied electrophysiologically in a model of human absence seizures: rhythmic metrazol activity (RMA) in rats. The effects of Ro 16-6028 pretreatment (0.01, 0.05, or 0.1 mg/kg intraperitoneally, i.p.) were compared with those of clonazepam (CZP, 0.02 or 0.1 mg/kg i.p.), valproate (VPA, 200, 300, or 400 mg/kg) and ethosuximide (ESM, 31.25, 62.5, or 125 mg/kg i.p.) in 45 rats with implanted electrocorticographic electrodes. RMA was elicited by an injection of pentylenetetrazol (metrazol, PTZ) in a dose of 40 or 35 mg/kg i.p. The effects of Ro 16-6028 were similar to those of CZP and VPA, i.e., suppression of RMA episodes, an increase in latency and a decrease in number, and total as well as mean duration. On the other hand, ESM differed from these antiepileptic drugs (AEDs) in inability to shorten the duration of RMA episodes. Based on these results, Ro 16-6028 might be predicted to be efficient against human absence seizures.
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PMID:Effects of a benzodiazepine, bretazenil (Ro 16-6028), on rhythmic metrazol EEG activity: comparison with standard anticonvulsants. 824 69

A 49-year-old man was admitted to our hospital because of epileptic seizures and memory dysfunction. He had been experiencing seizures several times a day since the age of 43 years. Despite antiepileptic drug therapy (sodium valproate [VPA] and clonazepam [CZP], he suffered from frequent complex partial seizures originating in the temporal lobe, and he had a memory disturbance since age 47. When carbamazepine (CBZ) was substituted for VPA and CZP, the epileptic seizures stopped and the memory disturbance improved. Noninvasive regional cerebral blood flow (rCBF) measurements using 99mTc-HMPAO-SPECT imaging were performed twice. The initial measurements on admission showed overall decreased rCBP that was more prominent in the cerebral cortex than in the subcortical nuclei. A follow-up SPECT examination after clinical improvement revealed a marked overall increase in rCBF, especially in the cerebral cortex. The SPECT findings suggest that the memory disturbance in this patient may have been associated with the overall cerebral blood hypoperfusion. This overall hypoperfusion can be attributed to the frequent complex partial seizures and/or the adverse effect of VPA and CZP. SPECT can provide important information suggesting the pathogenesis of memory disturbance associated with epilepsy.
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PMID:[A patient with epilepsy manifesting reversible memory dysfunction--a neuropsychological, electroencephalographical and radiological study]. 912 44

Clinical features of refractory epilepsy in children are symptomatic localization-related epilepsy, especially frontal lobe epilepsy, the onset in young age less than 3 years-old, and complication of developmental retardation. The treatments usually start with one drug of choice for specific seizure type. In the idiopathic epilepsy group, valproic acid was effective in 82% of the patients with generalized epilepsy and in 45% of localization-related epilepsy while carbamazepine was effective in 71% and 67%, respectively. However, in the refractory group which did not react to the drugs of choice at the initial treatment and continued to have seizures, no specific drugs were effective. Therefore, various kind of drugs, new or old, should be tried in sequence irrespective of the type of seizures. The seizure control was attained only in 10% (in the cases of CZP), and 17% (CLB) in localization-related epilepsy and in 9% (VPA), 12% (NZP) and 20% (ZNS) in generalized one in the refractory group. Although new drugs developed, the patients with refractory epilepsy do not tend to decrease in frequency and overall management including daily life or surgical therapy is mandatory for the children with refractory epilepsy.
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PMID:[Clinical features and treatment of refractory epilepsy in children]. 1223 5

Until now, a character of interactions among the antiepileptic drugs (AEDs), in some experimental models of epilepsy, has been determined alternatively with subthreshold and isobolographic methods. In order to elicit the precise and adequate method for evaluating two drug interactions, the comparative study was performed in the maximal electroshock-induced seizure test in mice. In this experimental model, the exact types of interactions among oxcarbazepine (OXC) and conventional AEDs (diphenylhydantoin, phenobarbital, valproate, carbamazepine, and clonazepam) were determined with both methods. Results from the subthreshold method showed a considerable reduction of ED(50) values of clonazepam, diphenylhydantoin and valproate (after administration of OXC at the highest subthreshold dose of 2.5 mg/kg), whilst ED(50)s of carbamazepine or phenobarbital were almost unchanged when OXC (2.5 mg/kg) was co-administered with these AEDs. Results from the 2-dimensional (2-D) isobolographic analysis of interactions for a 50% anticonvulsant effect, for three fixed drug dose ratio combinations of 1:2, 1:1, and 2:1, indicate antagonism between OXC and diphenylhydantoin as regards their anticonvulsant (protective) activity. Furthermore, the interactions between OXC and clonazepam occurred either antagonistic (for the fixed-ratios of 1:4 and 1:3) or synergistic (for the fixed-ratio combinations of 1:1 and 2:1) depending on the proportions of used drugs. Remaining interactions between OXC and carbamazepine, OXC and valproate, or OXC and phenobarbital (for the fixed-ratios of 1:3, 1:1, and 3:1) were isobolographically additive for a 50% anticonvulsant effect tested. The 3-dimensional (3-D) isobolographic analysis of interactions between OXC and CZP revealed that the dual character of interactions (antagonistic and synergistic) observed for a 50% anticonvulsant effect (ED(50)) was also present for additional drug-dose effects tested, i.e. ED(16) and ED(84). The 3-D isobologram for the combination of OXC with CZP clearly visualized either synergy or antagonism between the drugs in combinations.Distinct differences resulting from two experimental methods prove evidently the superiority of isobolographic analysis over the subthreshold method. The former clearly and adequately detects the exact types of interactions between two AEDs, becoming a potent and powerful paradigm for further studies evaluating the character of interactions among AEDs.
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PMID:Isobolographic and subthreshold methods in the detection of interactions between oxcarbazepine and conventional antiepileptics--a comparative study. 1452 51

This study examines the effect of acute administration of caffeine sodium benzoate (CAF) on the anticonvulsant action of four conventional antiepileptic drugs (AEDs: clonazepam - CZP, ethosuximide - ETS, phenobarbital - PB and valproate - VPA) against pentetrazole (PTZ)-induced clonic seizures in mice. The results indicate that CAF at a dose of 92.4 mg/kg significantly reduced the threshold for PTZ-induced clonic seizures in mice from 69.5 to 51.7 mg/kg (p<0.05), being ineffective at lower doses of 69.3 and 46.2 mg/kg. Moreover, CAF at doses of and 92.4 mg/kg attenuated the protective action of ETS against PTZ-induced seizures, by increasing its median effective dose (ED50) from 127.7 to 182.3 (p<0.05), and 198.3 mg/kg (p<0.01), respectively. In this case, no pharmacokinetic changes in total brain ETS concentrations after systemic ip administration of CAF (at 92.4 mg/kg) were observed, indicating a pharmacodynamic nature of interaction between ETS and CAF in the PTZ-test in mice. In contrast, CAF (at a dose of 92.4 mg/kg reducing the threshold for PTZ-induced seizures) combined with other AEDs (CZP, PB and VPA) did not affect their anticonvulsant action in the PTZ test in mice. Moreover, CAF (92.4 mg/kg) did not alter significantly total brain concentrations of the remaining AEDs (CZP, PB and VPA). The evaluation of potential acute adverse effects produced by AEDs in combination with CAF revealed that neither CAF (up to 92.4 mg/kg) administered alone nor combined with the studied drugs (at doses corresponding to their ED(50) values in the PTZ-test) affected motor performance of animals in the chimney test. In conclusion, the acute exposure to CAF may diminish the antiseizure protection offered by ETS in epileptic patients. Therefore, patients treated with ETS should avoid CAF.
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PMID:Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice. 1708 57


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