Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Labelled amino acids, 14C-leucine, 3H-glycine, 14C-GABA, 14C-glutamic acid and 14C-aspartic acid were applied to the surface of the cat's auditory cortex in dried filter paper strips for 40 min. The distribution of the amino acids taken up by the cortex was examined by autoradiography.The right acoustic area was stimulated by 2 cps acoustic clicks, through an ear-phone. Leucine showed cellular localization which was considerably dispersed by cortical excitation. Glycine was concentrated in nerve cells, mainly in layers I-II, but excitation intensified and extended its incorporation. GABA was accumulated rather diffusely in layers I-II with scattered cellular labelling which was depressed by stimulation. Glutamic and aspartic acids did not show any characteristic distribution pattern. The authors emphasize that the incorporation of glycine seems to be a good indicator of neurons being in excitation. The localizations of GABA uptake shows close correlation with the site of its physiological action.
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PMID:Incorporation of labelled amino acids into the acoustic cortex of the cat. 55 Jun 60

We report long-term clinical, neurochemical, and electrophysiologic data of gamma-vinyl GABA (GVG, vigabatrin) in three groups of patients. GVG was started as add-on therapy for 75 patients with refractory complex partial seizures (group A) and for 36 mentally handicapped patients with severe epilepsy (group B). The third group (C) consisted of 20 patients with carbamazepine (CBZ) monotherapy, in half of whom GVG monotherapy was substituted. After 3 months, 55% of patients in group A and 42% in group B were responders (reduction in seizure frequency greater than 50%). After 6 (group A) and 3 years (group B) of follow-up, 27 and 33% of the patients, respectively, still had good response to GVG. Neurochemical measurements showed a twofold increase in CSF GABA concentrations and minimal or no changes in other neurotransmitter-related parameters. In group C, substitution of GVG as medication tended to normalize the lengthened latencies in somatosensory evoked potentials (SEPs) observed during CBZ treatment.
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PMID:Gamma-vinyl GABA (vigabatrin) in epilepsy: clinical, neurochemical, and neurophysiologic monitoring in epileptic patients. 139 36

We have selected a strain of rats and designated it the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this strain, 100% of the animals present recurrent generalized non-convulsive seizures characterized by bilateral and synchronous spike-and-wave discharges accompanied with behavioural arrest, staring and sometimes twitching of the vibrissae. Spontaneous SWD (7-11 cps, 300-1,000 microV, 0.5-75 sec) start and end abruptly on a normal background EEG. They usually occur at a mean frequency of 1.5 per min when the animals are in a state of quiet wakefulness. Drugs effective against absence seizures in humans (ethosuccimide, trimethadione, valproate, benzodiazepines) suppress the SWD dose-dependently, whereas drugs specific for convulsive or focal seizures (carbamazepine, phenytoin) are ineffective. SWD are increased by epileptogenic drugs inducing petit mal-like seizures, such as pentylenetetrazol, gamma-hydroxybutyrate, THIP and penicillin. Depth EEG recordings and lesion experiments show that SWD in GAERs depend on cortical and thalamic structures with a possible rhythmic triggering by the lateral thalamus. Most neurotransmitters are involved in the control of SWD (dopamine, noradrenaline, NMDA, acetylcholine), but GABA and gamma-hydroxybutyrate (GHB) seem to play a critical role. SWD are genetically determined with an autosomal dominant inheritance. The variable expression of SWD in offsprings from GAERS x control reciprocal crosses may be due to the existence of multiple genes. Neurophysiological, behavioural, pharmacological and genetic studies demonstrate that spontaneous SWD in GAERS fulfill all the requirements for an experimental model of absence epilepsy. As the mechanisms underlying absence epilepsy in humans are still unknown, the analysis of the genetic thalamocortical dysfunction in GAERS may be fruitful in investigations of the pathogenesis of generalized non-convulsive seizures.
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PMID:Genetic absence epilepsy in rats from Strasbourg--a review. 151 94

1. To evaluate the relationship between the clinical response and enhancement of GABAergic neurotransmission, for 6 months we administered vigabatrin (gamma-vinyl-GABA, GVG) to 75 patients with complex partial epilepsy. Total GABA (TGABA), free GABA (FGABA), homocarnosine (HC), and GVG concentrations were measured in CSF of these patients before and during GVG treatment. 2. Over 50% reduction in seizures was found in 55% of the patients. Dose-reduction resulted in a relapse, i.e. the return of seizures. 3. At baseline TGABA, FGABA, and HC did not differ in responders and nonresponders. After GVG treatment, the TGABA and HC levels were lower in nonresponders (P less than 0.001), but the GVG and FGABA levels did not differ. The GVG dose reduction resulted in a concomitant decrease in TGABA, FGABA, HC and GVG (P less than 0.001). 4. According to our results GVG is an effective anticonvulsant drug in complex partial seizures. In nonresponders the poor anticonvulsant response may be related to the lower elevation of the CSF markers of GABAergic neuronal activity in this group compared with the responders.
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PMID:Cerebrospinal fluid GABA and seizure control with vigabatrin. 275 14

A study was conducted to assess the impact of single dosing and different dosing intervals of vigabatrin [gamma vinyl GABA (GVG)] in 11 patients with drug-resistant complex partial seizures. Cerebrospinal fluid (CSF) concentrations of total GABA, free GABA, homocarnosine, homovanillic acid (HVA), GVG, and 5-hydroxyindolacetic acid were measured up to seven days after a single dose. GVG levels were maximal within 24 h, suggesting that GVG acts to inhibit GABA-transaminase, and may also increase biogenic amines.
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PMID:Pharmacokinetic effects of vigabatrin on cerebrospinal fluid amino acids in humans. 276 13

Kindling is an animal model of epilepsy produced by focal electrical stimulation of the brain. This chapter: describes the kindling phenomenon; considers the validity of kindling as an animal model and proposes a hypothesis as to how kindling might contribute to human epileptogenesis; presents a critical review of current insights into the underlying mechanisms; and emphasizes that, if progress is to be made in understanding the mechanisms, the network of brain structures underlying kindling must be elucidated. Recent investigations directly related to the network issue are considered, namely studies demonstrating that a brainstem structure, the substantia nigra (SN), can regulate the kindled seizure threshold. Thus, either microinjection of a GABA receptor agonist or a GABA transaminase inhibitor into SN, but not into nearby sites, elevates kindled-seizure threshold. Likewise, destruction of SN, but not of adjacent structures, is associated with an increase of kindled-seizure threshold. These treatments suppress not only clonic motor seizures, but also complex partial seizures and afterdischarge at the site of stimulation. These findings demonstrate that the SN can regulate the intrinsic neuronal excitability of forebrain structures. A hypothesis is advanced that generation of a complex partial seizure requires activation of neurons in the SN which in turn feed back through polysynaptic connections to influence neurons at the site of seizure origin. This nigral influence on neurons at the site of seizure origin is either a direct excitation or a disinhibition. Thus, the seizure represents reverberatory activity within a network of brain structures which includes the SN. Other investigators have proposed that the centrencephalic system subserved seizure propagation; the relationship of the hypothesis proposed here to these earlier ideas is discussed.
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PMID:Kindling model of epilepsy. 287 21

The effect of gamma-vinyl GABA (GVG) on the interictal electroencephalogram (EEG) was studied in 13 patients with intractable complex partial seizures who participated in a single-blind, add-on, multicenter clinical trial of GVG. Precise operational definitions of epileptiform paroxysms were used to evaluate records before and after 3 months and 1 year of treatment with GVG. After 3 months of treatment, six patients exhibited reduction of both epileptiform paroxysms and seizure frequency, four had no change in seizure frequency nor in the EEG, and three had a reduction in seizure frequency but no concomitant reduction of epileptiform paroxysms in the EEG. Ten patients remained in the study after 1 year of treatment. In 4 patients both seizure frequency and EEG epileptiform paroxysms continued to decrease, in 1 patient both seizure frequency and number of EEG paroxysms increased, and in the remaining 3 there was no correlation between seizure frequency and EEG changes.
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PMID:Effect of gamma-vinyl GABA on interictal spikes and sharp waves in patients with intractable complex partial seizures. 291 22

The effects of gamma-vinyl GABA (GVG) and carbamazepine (CBZ) monotherapy on somatosensory (SEP) and visual (VEP) evoked potentials and spectral quantitative EEG (QEEG) were studied in 17 patients with complex partial seizures using a cross-over double-blind study design. CBZ was associated with statistically significant prolongation of SEP latencies. When the drug was switched to GVG, shortening of the peak latencies was observed. Prolonged pattern-VEP peaks were observed both during CBZ and GVG monotherapies. A similar but more subtle tendency of the peaks was observed in P100 latencies. Spectral EEG revealed a slowing of the occipital rhythm with CBZ. No QEEG changes related to GVG were found. The use of multimodal evoked potentials and QEEG should be considered in studying the effects of new antiepileptic drugs (AEDs).
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PMID:Electrophysiologic effects of gamma-vinyl GABA and carbamazepine. 292 44

The effects of three specific GABA receptor agonists, muscimol, progabide, and gaboxadol, on kindled seizures were evaluated in amygdala-kindled rats. The only compound that exerted significant anticonvulsant effects at nonsedative doses was progabide. Thus, after i.p. administration of 100 mg/kg progabide, a significant increase in seizure latency and significant decreases in duration of motor seizures and amygdala afterdischarges were determined. A decrease in severity of motor seizures was found only after 200 mg/kg progabide which, however, gave rise to marked sedation and muscle relaxation. Muscimol and gaboxadol were almost inactive in attenuating kindled seizures even at doses that produced pronounced side effects. Assuming that the amygdala-kindled rat is a useful model of complex partial seizures with secondary generalization in the human, the data suggest that GABA receptor agonists are not effective against this type of epilepsy (muscimol, gaboxadol) or effective only at large doses (progabide).
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PMID:Evaluation of different GABA receptor agonists in the kindled amygdala seizure model in rats. 299 Sep 87

Amygdala-kindled female rats were used to compare the effects of seven antiepileptic drugs that are clinically used for treatment of partial epilepsy with complex symptomatology, on generalized seizures, focal seizures, or electrographic seizure activity at the focus. As a second approach of drug evaluation, drug effects on mean latency, severity, and duration of the seizures were determined. Anticonvulsant potencies obtained were compared with those determined in the maximal electroshock seizure test in female rats. Phenobarbital, phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, but not primidone dose-dependently suppressed generalized motor seizures in kindled rats; however, except for the benzodiazepines, ED50S were substantially higher than those determined in the maximal electroshock seizure test. Compared with their effect on generalized motor seizures, all drugs were much less potent in blocking focal seizures and afterdischarges recorded from the amygdala. The data suggest that with respect to behavioral and pharmacologic characteristics of the amygdala kindling model, fully kindled rats may be a useful model for drug-resistant complex partial seizures with secondary generalization. Results of experiments with novel inhibitors of GABA uptake, which were inactive in the maximal electroshock seizure test but highly potent against kindled seizures, suggest that such drugs might be more effective than current antiepileptic drugs for treatment of partial epilepsy.
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PMID:Is amygdala kindling in rats a model for drug-resistant partial epilepsy? 308 32


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