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)

Gabapentin was studied as an open-label 'add-on' antiepileptic drug in 35 patients with partial seizures. Follow-up at 6 months, 12 months, 18 months, and 24 months is reported. There was a trend toward improvement in simple (SPS) and complex partial seizures with it reaching significance for SPS at 12 and 24 months and for the weighted combination of seizures at 3 months. Five of nine patients were subsequently successfully converted to gabapentin monotherapy. Of those five, one is now seizure free and three are significantly improved since baseline. One remains with unchanged seizure frequency compared to baseline, but is experiencing less toxicity than at that time. This long-term observation suggests that the short-term effect demonstrated in blinded studies continues and that indeed some patients with refractory epilepsy can be maintained on gabapentin alone. Based on these findings, double-blind monotherapy trials of this drug are presently being conducted.
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PMID:Long-term treatment with gabapentin for partial epilepsy. 146 1

Forty-three patients completed a double-blind, placebo-controlled study of Gabapentin (GBP) as add-on therapy in partial and secondarily generalized seizures. All patients were followed for an initial 3-month baseline period, after which they were randomly allocated to receive either a placebo or 900 or 1,200 mg/day GBP for 3 months. A statistically significant difference in seizure frequency from the baseline to the treatment phase was noted between patients receiving placebo and GBP 1,200 mg, in whom seizure frequency decreased 57%. The GBP dosage of 900 mg appeared to be ineffective. A close relationship was observed between the serum GBP concentrations and the GBP dosage based on the seizure frequency. Serum GBP concentrations greater than 2 micrograms/ml resulted in a lower frequency of seizures. The adverse effects were minor and consisted mainly of transient drowsiness. GBP appears to be effective in the treatment of partial epileptic seizures in a dosage-related manner.
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PMID:Double-blind study of Gabapentin in the treatment of partial seizures. 190 7

Gabapentin exerts anticonvulsant effects in different animal models of seizure states and in epileptic patients with different seizure types, but the mechanism of action of these effects is unknown. In the present study, the gamma-aminobutyric acid (GABA) accumulation induced by aminooxyacetic acid (AOAA) was used as a method to study the effects of gabapentin on regional turnover of GABA in the rat brain. Gabapentin was administered at a dose of 23 mg/kg i.p. (the ED95 against tonic electroconvulsions in rats) 1, 2 and 8 h prior to injection of AOAA, 100 mg/kg, i.p. Gabapentin significantly increased the AOAA-induced GABA accumulation in most of the 12 brain regions examined, but the time course of the increases in GABA accumulation differed from region to region. Regions in which the time course of the increase in GABA accumulation was similar to the anticonvulsant time course of gabapentin included substantia nigra, amygdala and thalamus. The data suggest that an effect of gabapentin on GABA synthesis might be involved in its mechanism of anticonvulsant action.
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PMID:Gabapentin increases aminooxyacetic acid-induced GABA accumulation in several regions of rat brain. 194 36

Gabapentin is an analogue of gamma aminobutyric acid (GABA) which has anticonvulsant properties in animals. In a multicentre, double-blind, placebo-controlled, parallel-group study of 1200 mg/day gabapentin as additional therapy in 127 patients with drug-resistant partial epilepsy, 25% of patients who received gabapentin had the number of partial seizures at least halved, compared with 9.8% of patients given placebo. The median reduction in partial seizure frequency during 12 weeks' treatment was 29.2% with gabapentin compared with 12.5% with placebo. The mean adjusted response ratio for gabapentin (-0.192) was significantly better than the ratio of -0.060 for placebo by analysis of variance. 62% of patients who received gabapentin reported mostly mild or moderate adverse effects compared with 41% on placebo; no interactions were observed between gabapentin and other standard anticonvulsants. Gabapentin is an effective additional treatment for patients with partial epilepsy refractory to standard therapy, is fairly well tolerated, and appears to have a favourable efficacy-to-toxicity ratio.
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PMID:Gabapentin in partial epilepsy. UK Gabapentin Study Group. 197 62

Gabapentin (GBP) is a cyclic gamma-aminobutyric acid (GABA) analog and investigational antiepileptic drug which is effective in the treatment of a variety of human and experimental seizures. GBP's antiepileptic mechanism of action is not known. The present studies tested for effects of GBP on inhibitory (GABA and glycine) and excitatory (N-methyl-D-aspartate (NMDA) and non-NMDA) amino acid neurotransmitter receptors, on repetitive firing of sodium (Na+) action potentials, and on voltage-dependent calcium (Ca2+) channel currents in cultured rodent neurons using intracellular, whole cell, or single channel recording techniques. GBP did not have a significant effect in any experiment when tested at or above concentrations that are therapeutic in humans except for a variable enhancement of NMDA-evoked depolarizations. These results suggest that the antiepileptic activity of GBP is not due to direct effects at receptors for inhibitory or excitatory amino acids or on voltage-dependent Na+ or Ca2+ channels.
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PMID:Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons. 750 42

There are several new antiepileptic drugs undergoing extensive clinical investigation. Five new drugs--vigabatrin, lamotrigine, gabapentin, felbamate and oxcarbazepine--appear to be the most widely tested and promising agents. Vigabatrin is most effective in drug-resistant partial epilepsy. Vigabatrin is also effective in infantile spasms, but seems to have negative effects on myoclonic epilepsies and absence seizures. Lamotrigine and felbamate seem to be effective in partial epilepsy and in Lennox-Gastaut syndrome. In addition, lamotrigine and felbamate seem to have efficacy in idiopathic generalised epilepsies. Oxcarbazepine appears to be equally as effective as carbamazepine, but less toxic. Gabapentin has few adverse effects and has efficacy in some patients with drug-resistant partial epilepsy. Some of the new antiepileptic drugs modify excitatory or inhibitory amino acid transmission, but some of them may employ new, still unknown mechanisms of action. Depending on the mechanism of action, the therapeutic effectiveness of the antiepileptic drugs may differ in specific epileptic syndromes. Future antiepileptic drugs may thus give us the possibility to design rational polypharmacy for individual patients by combining agents with different spectra of effectiveness. Considering the goal of good tolerability in the development of the new antiepileptic drugs, polypharmacy with these agents is not expected to increase adverse effects significantly.
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PMID:Place of newer antiepileptic drugs in the treatment of epilepsy. 751 Jun 9

Significant advances have been made in understanding the molecular and cellular mechanisms underlying seizure disorders and the actions of antiepileptic drugs. Agents with new mechanisms of action or enhanced activity via known mechanisms might provide improved seizure control or more selective therapy for specific epilepsies. Gabapentin is a new antiepileptic drug that is structurally similar to the neurotransmitter GABA and the endogenous amino acid L-leucine. The mechanism of action of gabapentin is not fully understood, but its distinct profile of anticonvulsant activity in animal seizure models and its lack of activity at many drug binding sites associated with other antiepileptic drugs indicate that its mechanism of action is novel.
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PMID:Emerging perspectives on the mechanism of action of gabapentin. 751 15

Gabapentin (Neurontin--Parke-Davis) is a new antiepileptic drug. Like lamotrigine, which we reviewed 2 years ago, it is marketed for the add-on treatment of patients with partial or secondarily generalised (tonic-clonic) seizures that are inadequately controlled with standard antiepileptic drugs.
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PMID:Gabapentin--a new antiepileptic drug. 763 23

Gabapentin is an antiepileptic drug with an unknown mechanism of action apparently dissimilar to that of other antiepileptic agents, and possessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminishing the likelihood of drug interactions with other antiepileptic agents and drugs such as oral contraceptives. Although gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with partial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day) provides notable benefit, reducing seizure frequency by > or = 50% in 18 to 28% of patients with refractory partial seizures, as shown in 3 double-blind, placebo-controlled trials. Overall, seizure frequency decreased by 18 to 32% during 3-month treatment periods. Patients with complex partial seizures, and partial seizures secondarily generalised, are particularly likely to respond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly somnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated when administered to a few patients for periods of up to 5 years, its long term tolerability profile has yet to be fully expounded. Thus, with its favourable pharmacokinetic profile, and efficacy in some refractory patients, gabapentin is poised to fill a niche as an adjunct to the treatment of partial epilepsy. Promising results obtained thus far warrant further work to clarify its long term tolerability, its possible efficacy in other seizure types, its position relative to other agents and its use as monotherapy. In the meantime, gabapentin is likely to provide a much-needed option in a therapeutic area requiring complex management.
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PMID:Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. 769 32

Gabapentin represents a significant advance in the management of epilepsy. To date, it appears to be most useful as an add-on therapy for patients with partial seizures uncontrolled by standard anticonvulsants. Side effects are mild and often subside with continued therapy. Unlike traditional anticonvulsants, gabapentin lacks significant drug interactions.
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PMID:Gabapentin (NEURONTIN)--a novel anticonvulsant. 772 98


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