Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anticonvulsant potency and neurological toxicity of two new catalytic inhibitors of GABA-transaminase have been assessed in acute experiments in baboons with a natural syndrome of photic epilepsy. gamma-Acetylenic GABA, 160--200 mg/kg, or gamma-vinyl GABA, 450--950 mg/kg, intravenously, gave complete protection against generalised myoclonus or seizure responses induced by photic stimulation (in baboons without or with priming with subconvulsant doses of allylglycine). The protection became maximal 1--3 h after injection, and continued for 7--24 h. Signs characteristic of the acute toxicity of anticonvulsant drugs (nystagmus and ataxia) were not seen. The potential use of these compounds in human epilepsy deserves investigation.
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PMID:Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid). 10 Aug 12

The most potent agents currently available for suppressing myoclonic activity in animals and humans act to enhance GABA-mediated inhibition and/or to diminish amino acid-induced excitation. Postsynaptic GABA-mediated inhibition plays an important role at the cortical level, diminishing the effect of augmented afferent activity and preventing pathologically enhanced output. Enhancement of GABAergic inhibition, principally at the cortical level but also at lower levels, by clonazepam and by valproate appears to be a predominant element in their antimyoclonic action. Studies in various animal models, including photically induced myoclonus in the baboon, P papio, indicate the value of other approaches to enhancing GABA-mediated inhibition. Among such approaches meriting evaluation in humans are inhibition of GABA-transaminase activity by gamma-vinyl GABA and action at some of the benzodiazepine receptors to enhance the action of GABA, as by the novel anticonvulsant beta-carbolines. Excitatory transmission mediated by dicarboxylic amino acids appears to play a role in myoclonus, especially at the spinal level, but also in the brainstem, cerebellum, basal ganglia, and cortex. Among various novel agents that act at the postsynaptic receptor site to antagonize such excitation, those specifically blocking excitation induced by aspartate and/or NMDA prevent myoclonic activity in a wide range of animal models. Further research is required before such agents can be evaluated in humans.
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PMID:Drugs acting on amino acid neurotransmitters. 286 23

GABAergic agents have been evaluated for acute anticonvulsant activity in baboons, Papio papio with photosensitive epilepsy. The potent GABAA agonists muscimol and THIP are proconvulsant. (-)Baclofen, 2 mg/kg suppresses myoclonic responses; higher doses facilitate EEG paroxysmal activity. (S) gamma-vinyl GABA, 100-200 mg/kg, suppresses myoclonic responses for more than 24 h. Some derivatives of esters of beta-carboline-3-carboxylate that bind to the benzodiazepine receptor, e.g. ZK 91296 and ZK 93423, suppress myoclonus with a potency at least as great as diazepam.
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PMID:GABAergic agents as anticonvulsants in baboons with photosensitive epilepsy. 608 55

In the context of a study of the effects of gamma-vinyl-GABA (GVG) on seizure occurrence and on EEG abnormalities we present three cases with focal epilepsy in which new clinical and EEG paroxysmal manifestations were observed during GVG therapy. At that time, whereas an amelioration or no change in patients' habitual seizures were observed, myoclonic jerks appeared with related changes in the EEG paroxysmal abnormalities, represented by generalized polyspike and wave complexes. An electroclinical correlation was recorded in one case. These data indicate that, although occurring rarely, it is possible to have epileptic myoclonus during GVG treatment. Mechanisms underlying these manifestations are difficult to explain. Probably a shift in the anti/proconvulsant GABAergic balance towards the latter may compromise the therapeutic effect of GVG.
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PMID:Development of myoclonus in patients with partial epilepsy during treatment with vigabatrin: an electroencephalographic study. 773 67

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