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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a double-blind cross-over add-on trial an average daily dose of 2100 mg progabide or placebo were given for 3 months each as adjunctive therapy to 11 patients with intractable complex partial seizures uncontrolled by a high-dose regimen of either carbamazepine, phenobarbital, phenytoin or primidone. A reduction or an increase in seizure frequency by more than 50% was seen in one patient each. Mild transient sedative side effects were observed in two patients. The plasma concentrations of the concomitant antiepileptic drugs remained unchanged. Progabide appears to be as effective as primary antiepileptic drug for adjunctive therapy in partial epilepsy refractory to previous high-dose therapy. Progabide does not seem to be the drug urgently needed for failures of standard therapy despite its few side effects.
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PMID:Progabide as an add-on drug for epilepsy refractory to high dose antiepileptic drug therapy. 638 68

Progabide (SL 76002) was studied in a randomized double-blind crossover trial using 20 outpatients suffering from partial complex seizures. Progabide was added to the concomitant antiepileptic treatment in a fixed dosage schedule. The design included an open therapy control unit. No significant difference was established between the number of partial seizures during treatment with progabide and placebo. A trend was observed for lower seizure frequency of secondary generalized seizures during treatment with progabide. Only mild and transient side effects were observed. There was no difference between the side effects of progabide and placebo.
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PMID:Progabide: a controlled trial in partial epilepsy. 640 42

The anticonvulsant properties of the specific GABA receptor agonist, progabide, were evaluated in the kindled amygdaloid seizure model in rats. Progabide attenuated afterdischarge durations and the severity of the accompanying convulsive responses in previously kindled rats. This effect occurred only at doses that also produced sedation and ataxia. When administered daily during kindling acquisition, progabide increased the number of trials necessary to complete kindling. The duration and severity of responses induced by stimulations during the acquisition period were reduced in a dose-dependent manner. In spite of these changes during the acquisition period, all subjects exhibited kindled behavior comparable to that of controls when they had accrued the same total afterdischarge experience. In light of these and other data regarding the GABA system and its influences on kindling, we conclude that GABA acts nonspecifically to attenuate various seizure states. It appears that GABA plays no major role in the mechanisms actually responsible for kindling development.
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PMID:An analysis of the actions of progabide, a specific GABA receptor agonist, on kindling and kindled seizures. 669 Mar 14

Pretreatment of rats with homotaurine (3 aminopropanesulfonic acid; 3APS), a synthetic gamma-aminobutyric acid (GABA) analog, protected from the convulsant and cytotoxic action of systemically injected kainic acid (KA). Wet dog shaking (WDS) behavior was significantly reduced. Taurine, an inhibitory non-GABA-mimetic amino acid, and muscimol (another direct GABA-agonist) reduced the number of seizures and lesions in the brain but were less effective than homotaurine. Progabide (a GABA-agonist) did not modify kainic acid effects. The neurotoxicity of kainic acid could have been due to repetitive convulsive activity. Activation of GABA-mediated inhibition is an effective, but not the determinant means of preventing KA-induced abnormalities.
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PMID:Homotaurine (3 aminopropanesulfonic acid; 3APS) protects from the convulsant and cytotoxic effect of systemically administered kainic acid. 719 33

The effects of the GABAergic drugs nipecotic acid, Gabrene, baclofen and metatolylcarbamide (MTC), when given alone or in combination at subthreshold doses with AT II also at a subthreshold dose effective on PTZ-kindling in mice were studied. PTZ-kindling was provoked by intraperitoneal (i.p.) injections of PTZ (40 mg/kg) every other day in male albino mice until clonic seizures appeared. Nipecotic acid (100 and 200 micrograms/mouse intracerebroventricularly [i.c.v.]) tended to decrease seizure intensity. Gabrene (25, 50, 100 and 250 mg/kg i.p.) inhibited PTZ-kindled seizures. Baclofen at a doses of 2.5 and 5 mg/kg i.p. tended to decrease seizure intensity and at a dose of 10 mg/kg was ineffective at all. MTC (50 and 75 mg/kg i.p.) tended to decrease and at a dose of 100 mg/kg significantly decreased seizure intensity. Combinations of subthreshold dose of AT II (0.05 micrograms/mouse i.c.v.) and subthreshold doses of nipecotic acid (100 micrograms/mouse) or Gabrene (10 mg/kg) or baclofen (10 mg/kg) or MTC (50 mg/kg) significantly decreased the intensity of PTZ-kindled seizures in mice. The observed potentiation of the anticonvulsive activity on PTZ-kindling suggests interactions of AT II receptors with GABA receptors (GABAA, GABAB or both), effected through allosteric mechanisms.
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PMID:Further evidence for the interactions between angiotensin II and GABAergic transmission in pentylenetetrazol kindling seizures in mice. 774 50

We made a comparative study of the anticonvulsant effect of GABA agonists on feline amygdala or hippocampal kindled seizures. Progabide (PGB) [gamma-aminobutyric acid (GABA) receptor agonist 25-100 mg/kg intraperitoneally, i.p.] significantly reduced both the kindled seizure stage and after discharge (AD) duration in a dose-dependent manner. SKF89976A (GABA uptake inhibitor 0.5-2.0 mg/kg i.p.) also significantly reduced the kindled seizure stage. Toxic doses of SKF89976A caused generalized paroxysmal EEG discharges and myoclonus, but AD generation in the kindled focus was suppressed completely. Furthermore, gamma-vinyl GABA (GABA catabolic enzyme inhibitor, GVG 50-200 mg/kg i.p.) significantly reduced the seizure stage, while causing prolongation of the AD duration. In contrast, baclofen (selective GABAB receptor agonist, 1 or 5 mg/kg) did not show anticonvulsant effects on any parameters of kindled seizures. Therefore, these GABA agonists, which potentiate the inhibitory function of the GABAA systems, have potent anticonvulsant effects on partial onset and secondarily generalized limbic seizures.
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PMID:Comparative study of the anticonvulsant effect of gamma-aminobutyric acid agonists in the feline kindling model of epilepsy. 824 67

The anticonvulsant action of three drugs facilitating GABAergic inhibition by different mechanisms (valproate, phenobarbital and progabide) was studied in 229 young rats (12, 18 and 25 days old) with implanted electrodes. Epileptic afterdischarges (ADs) elicited by electrical stimulation of the sensorimotor cortex were used as a model. All three drugs were able to suppress ADs, even the lowest doses used blocked the prolongation seen with repeated stimulations under control conditions. In addition to these general effects, some differences among the three drugs were observed: phenobarbital (10, 20, and 40 mg/kg i.p.) exhibited marked anticonvulsant action in all three age groups whereas valproate (200 and 400 mg/kg i.p.) was somewhat less effective in the youngest rats studied than in the two older groups. Progabide exhibited an effect similar to valproate when a higher dose (150 mg/kg i.p.) was taken into account, but the lower dose (75 mg/kg i.p.) was most efficient in 12 day old rat pups. Our data support the possibility that cortical ADs represent a model of human myoclonic seizures. In addition, they suggest an uneven development of individual components of the GABAergic inhibitory system.
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PMID:Suppression of cortical epileptic afterdischarges in developing rats by anticonvulsants increasing GABAergic inhibition. 895 14

The action of progabide against motor seizures elicited by pentylenetetrazol was studied in 7-, 12-, 18-, 25-day-old and adult rats. Progabide (dissolved in dimethylsulfoxide) was injected in doses from 12.5 to 150 mg/kg i.p. 30 min before pentylenetetrazol. Minimal seizures were not affected by solvent or progabide pretreatment. The action of progabide against major, i.e. generalized tonic-clonic seizures, changed with age: adult rats exhibited a tendency to suppression of whole major seizures, whereas specific suppression of the tonic phase was observed in rat pups during the first three weeks of life. The only effect seen in 25-day-old animals was prolongation of the latency of major seizures after the highest dose of progabide.
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PMID:Anticonvulsant effect of progabide in rats during ontogenesis. 972 21

The anticonvulsant action of SL 75 102, a metabolite of Progabide, was studied in a model of pentylenetetrazol-induced motor seizures in adult and 12-day-old rats. SL 75 102 suppressed generalized tonic-clonic seizures in adult rats and restricted the tonic phase of these seizures in rat pups. SL 75 102 was less effective than Progabide. In addition, some minor differences in anticonvulsant actions of these two drugs were observed.
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PMID:Anticonvulsant effect of SL 75 102 in adult and immature rats. 972 25

Antiepileptic drugs affect endocrine and immune system activity, however, it is not clear whether these effects are indirect, via interference with neurotransmitters, membrane receptors and ion channels or maybe independent of neuronal mechanisms. In order to shed more light on this problem, in the present study, we evaluated effects of some new-generation antiepileptic drugs and progabide as a GABA-mimetic on the corticosterone-induced chloramphenicol acetyltransferase (CAT) activity in mouse fibroblast cells stably transfected with mouse mammary tumor virus (MMTV)-CAT plasmid. Treatment of cells with felbamate for five days inhibited in a concentration-dependent manner (3-100 microM) the corticosterone-induced reporter gene transcription. Progabide and loreclezole also inhibited the corticosterone-induced CAT activity, but with lower potency, and significant effects were observed at 10 to 100 microM concentration. Tiagabine and stiripentol showed less potent inhibitory effect on functional activity of glucocorticoid receptors (GR). In contrast, topiramate and lamotrigine (3-100 microM) failed to affect the corticosterone-induced gene transcription. These data indicate that some new antiepileptic drugs and progabide may suppress glucocorticoid effects via the inhibition of GR-mediated gene transcription. In turn, attenuation of GR function could influence antiepileptic drug effect on seizures, neuronal degeneration and immune system activity.
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PMID:Effects of some new antiepileptic drugs and progabide on glucocorticoid receptor-mediated gene transcription in LMCAT cells. 1804 53


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