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)

NINE NEW MOLECULES: Since 1990, nine antiepileptic drugs have been launched in France: vigabatrin (Sabril), felbamate (Taloxa), gabapentin (Neurontin), lamotrigine (Lamictal), tiagabine (Gabitril), fosphenytoin (Prodilantin), topiramate (Epitomax), oxcarbazepine (Trileptal) and levetiracetam (Keppra). INDICATIONS EXTENDING: The indications for these new antiepileptic molecules, initially indicated in the case of insufficient efficacy or intolerance to first (phenobarbital, phenytoin) or second generation (valproate, carbamazepine) antiepileptics are in fact progressively extending, notably with the approval of first line monotherapy with gabapentin (partial epileptic seizures in adults), lamotrigine (partial and generalised epilepsy, and in addition in children) and oxcarbazepine (partial epilepsy). PROBLEMS OF TOLERANCE: Two molecules (vigabatrin and felbamate) had their prescription reduced because of rare but severe side effects, which had not been detected during the studies preceding marketing authorisation. The availability of these new antiepileptics has broadened and diversified but also complicated the medical management of epilepsy. Although the efficacy of the molecules has been demonstrated, particularly in certain specific indications, some products (felbamate, tiagabine, topiramate) exhibit an average efficacy/safety profile, whereas others (felbamate, lamotrigine) expose the patients to rare but potentially severe idiosyncratic effects. Moreover, some drugs with limited spectrum (vigabatrin, gabapentin, tiagabine and oxcarbazepine) may even worsen the symptoms of epilepsy. INTEREST AND LIMITS: The new antiepileptics often lead to remarkable results in cases of moderate epilepsy. However, they do not appear to change the conditions of the small percentage of patients who suffer from truly severe epilepsy. More targeted indications, notably in children, warrant specification in rigorous clinical trails that are still difficult to elaborate. All these data justify the efforts made in the development of new drugs, and the emergence of surgical and alternative approaches.
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PMID:[New epileptic treatments. Current modalities and their utilization]. 1271 20

Gabapentin was approved for use in the USA in 1994 as an add-on drug in adults who have partial seizures either alone or with secondary generalised seizures. Its use has been expanded to include treatment for other conditions such as neuropathic pain and paraesthesiae. Gabapentin was prescribed for our patient who had persistent left-sided hemi-paraesthesiae consequential of a previous thalamic infarct. One week after commencement of gabapentin, she developed an adverse reaction in the form of a purpuric rash over bilateral lower limbs. Skin biopsy revealed histological features of cutaneous leukocytoclastic vasculitis. This rash completely resolved with withdrawal of gabapentin and steroidal treatment. This cutaneous adverse reaction to gabapentin has not been reported in the medical literature.
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PMID:A case of cutaneous leukocytoclastic vasculitis associated with gabapentin. 1276 64

Benzodiazepines (BZDs) are the drug of choice for the suppression of alcohol withdrawal symptoms. Gabapentin, a drug approved for use as adjunctive therapy in the treatment of partial seizures, has none of the BZD-type difficulties (drug interactions, abuse potential). We retrospectively report on the use of gabapentin for ethanol withdrawal in 49 patients. Thirty-one patients were treated in the outpatient program and 18 in the general inpatient psychiatric unit. Positive outcomes as evidenced by completion of gabapentin therapy were achieved in 25 out of 31 outpatients and 17 out of 18 inpatients. Statistical significance was reached regarding the positive relationship between prior ethanol use and inpatient "as needed" benzodiazepine use. Both sets of data suggest that gabapentin works well for the mild to moderate alcohol withdrawal patient.
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PMID:Gabapentin for the treatment of ethanol withdrawal. 1276 80

The pharmacokinetics, efficacy, and adverse effects of gabapentin and lamotrigine, two new antiepileptic drugs (AEDs), are reviewed. Gabapentin and lamotrigine are promising advances in the treatment of epilepsy, which has not been satisfactorily controlled by available agents in 25-41% of patients. Gabapentin is chemically similar to gamma-aminobutyric acid, but it is able to pass into the central nervous system. It is effective for the treatment of partial-onset seizures that are refractory to other AEDs. It has no known drug-drug interactions and a relatively benign adverse effect profile, but its short half-life necessitates at least thrice-daily dosing. Lamotrigine is structurally unrelated to the other available AEDs. Its role is currently limited to add-on therapy in patients with partial seizures, with or without secondary generalization, that are resistant to current treatment. The efficacy of lamotrigine in patients with primary generalized tonic-clonic seizures, absence seizures, and Lennox-Gastaut syndrome remains to be validated. The adverse effect profile also remains to be determined. A rash may appear in up to 5% of patients, possibly necessitating discontinuation of the drug. Although lamotrigine does not seem to affect the pharmacokinetics of the other AEDs, the other AEDs affect lamotrigine pharmacokinetics. Lamotrigine can be given once or twice daily. Gabapentin and lamotrigine may be useful in treating patients whose epilepsy is not controlled by other available AEDs; however, further research is needed to confirm their roles in epilepsy treatment.
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PMID:Gabapentin and lamotrigine: novel antiepileptic drugs. 1287 25

Drosophila bang-sensitive (bs) mutants exhibit a stereotypic seizure and paralysis following exposure to mechanical shock. In a physiological preparation, seizures and failures corresponding to the defective behavior are observed in response to high frequency stimulation. The amplitude of the stimulus necessary to produce bs behavior, or seizure threshold, varies with bs mutant and its gene dosage. In many respects, the bs defects are similar to those observed in mammalian seizure disorders. Antiepileptic drugs (AEDs) were administered by feeding to easily shocked(2) (eas(2)), a representative bs mutant. The mean recovery times of treated flies were examined in comparison to control cultures. Some of the drugs administered, including carbamazeprine, ethosuximide, and vigabactrin, had little or no effect on the bs behavior of eas(2). Gabapentin, however, showed a reduction in mean recovery time with chronic drug exposure. Phenytoin also had a significant effect on the bs behavior of treated flies. There was a reduction of both mean recovery time and the percentage of flies that displayed bang-sensitive behavior with both acute and chronic treatment. The adult giant fiber preparation was used to examine the effects of phenytoin physiologically. Treated eas(2) flies showed changes in their response to normal stimulation as well as alterations in seizure threshold in response to high frequency stimulation. Gabapentin was also effective against two other bs mutants, bangsenseless(1) and slamdance(iso7.8), at strain-specific concentrations, while phenytoin also reduced bang-sensitive behaviors in bangsenseless(1) in a dose dependent manner. AEDs, therefore, can be used to dissect aspects of bs behavior and this model may be useful in understanding the underlying basis of seizure disorders.
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PMID:Treatment with the antiepileptic drugs phenytoin and gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive mutants. 1497 27

In this study for thirty (30) patients with alcohol withdrawal syndrome, the response to anticolvusant gabapentin was assessed. Thirty (30) patients with median age of 57.0 years and median body weight of 79.1 kg were treated with gabapentin 3 x 300 mg daily for up 30 days. The preliminary findings of this study suggest that gabapentin is very effective against tonic-clonic seizures in alcohol withdrawal syndrome. Gabapentin was safe and well tolerated. For twenty (20) patients no side effect were observed.
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PMID:A study of gabapentin in the treatment of tonic-clonic seizures of alcohol withdrawal syndrome. 1501 94

Hepatic clearance of chemotherapy drugs is increased by many antiepilepsy drugs. At our institution, new-onset seizures in children on chemotherapy are treated with gabapentin, a nonhepatic enzyme inducer. The charts of all children given gabapentin for seizures were reviewed. At a median follow-up of 34 months, seizures were controlled in 74% of 50 children given gabapentin monotherapy as initial treatment: 91% of the leukemia group, 57% of the brain tumor group, and 75% of the other tumor group. Seizures were controlled in 49% of 59 children in whom gabapentin was added to other antiepilepsy drugs: 43% of the leukemia group, 53% of the brain tumor group, and 50% of the other tumor group. More than one seizure at presentation, focal neurologic deficits, high-dose methotrexate, brain irradiation, and T2-weighted signal abnormality around the brain tumor cavity predicted uncontrolled seizures. Only 8 children (7%) reported adverse effects, and the drug was discontinued in two. Gabapentin effectively controls seizures in children receiving chemotherapy and is well tolerated.
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PMID:Gabapentin to control seizures in children undergoing cancer treatment. 1507 1

The primary goals of antiepileptic treatment are complete cessation of seizure without any adverse reaction. In adult refractory focal epilepsies, a rational approach is based on adequate syndromic categorization and accurate knowledge of the pharmacological properties of antiepileptic drugs, whose number has significantly increased in recent years. Since 1991 nine new antiepileptic medications have been marketed in France, i. e. by order of appearance, vigabatrin (Sabril), felbamate (Taloxa), gabapentin (Neurontin), lamotrigine (Lamictal), tiagabine (Gabitril), fosphenytoin (a water-soluble phenytoin prodrug, Prodilantin), topiramate (Epitomax), oxcarbazepine (Trileptal) and levetiracetam (Keppra). Efficacy of these new compounds in focal epilepsies is proven, and in some patients with middle-severity focal epilepsy, clinical benefit is significant. Improvement is especially significant in terms of tolerability, ease of use and reduced interaction potential. However, some of these drugs (tiagabine, topiramate) may have an unfavorable short-term tolerance profile, while others (felbamate, lamotrigine) expose patients to a potential risk of severe acute idiosyncratic reactions. Increased availability of new drugs and the fact that drug monitoring has been claimed to be of little or no value in newly-marketed drugs have paradoxically strongly complicated therapeutic options. Moreover, only a few patients with truly refractory focal epilepsy can be made seizure-free by these new compounds, and the search for more effective anticonvulsants should continue in addition with alternative therapies or surgery.
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PMID:[Treatment protocol for long-term anti-epilepsy drugs in adults with refractory partial epilepsy]. 1533 73

Pharmaceutical manufacturer Warner-Lambert has agreed to plead guilty and pay more then $430 million to resolve criminal charges and civil liabilities in connection with its Parke-Davis division's illegal and fraudulent promotion of unapproved uses for the drug Neurontin (gabapentin). The drug was approved by the Food and Drug Administration in December 1993 solely for use with other drugs to control seizures in people with epilepsy.
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PMID:Drug maker to pay $430 million in fines, civil damages. 1534 83

Gabapentin (GBP), an anticonvulsant drug, 10 mg/kg, i.p., but not 100 mg/kg, i.p., enhanced retention of an inhibitory avoidance task when given 20 min after training, as indicated by retention performance 48 h later. The immediate post-training administration of pentylenetetrazol (PTZ, 45 mg/kg, i.p.) impaired retention performance. The amnesic effects of the convulsant drug PTZ were not influenced by GBP at any level of doses. However, GBP 100 mg/kg, but not 10 mg/kg, delayed the latency to first clonic body seizures and decreased the duration of convulsion induced by PTZ. The enhancing effect of GBP on retention was not prevented by the opiate receptor antagonist, naltrexone (0.01 mg/kg, i.p.), which completely prevented the impairment of retention caused by PTZ. Further, naltrexone did not modify the convulsions induced by PTZ. In mice pretreated with naltrexone and that received PTZ, the administration of GBP again, enhanced retention performance during the retention test. Since previous results indicate that the amnesic action of PTZ are due to an effect on memory retrieval, the present results provide additional pharmacological evidence suggesting that GBP influenced memory consolidation and not memory retrieval of an inhibitory avoidance task in mice.
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PMID:Posttraining administration of pentylenetetrazol dissociates gabapentin effects on memory consolidation from that on memory retrieval process in mice. 1535 51


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