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

Muscimol, 0.25-1.0 mg/kg, i.v., was administered acutely to 4 adolescent baboons, Papio papio, that show photically induced epilepsy. On the EEG, slowing of background rhythms was associated with the appearance of spikes, polyspikes, and recurring symmetrical spike-wave complexes. These changes were maximal 0.5-2 hr after muscimol injection. Regular testing with intermittent light stimulation showed either no change from control responses or a more severe epileptiform EEG 0.1-3 hr after muscimol. Photically induced myoclonus was not modified by muscimol. Despite its GABA-abonist properties, muscimol is not an effective anticonvulsant.
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PMID:Electroencephalographic and behavioral effects of a GABA agonist (muscimol) on photosensitive epilepsy in the baboon, papio papio. 11 8

Compounds blocking the uptake of GABA into neurons or glia have been injected intracerebroventricularly (icv) or intraperitoneally (ip) in DBA/2 mice, age 21-28 days. Protection against audiogenic seizures was seen 30 min after the icv injection of (+)-2,4-diaminobutyric acid (0.5-2.0 mumoles), (+/-)-nipecotic acid (1.6-3.2 mumoles), (+)-ethyl nipecotate (0.4-0.8 mumoles), (-)-piperazic acid (4 mumoles) and putrescine (2 mumoles) or the ip injection of (+)-2,4-diaminobutyric acid (4-8 mmoles/kg and (+)-ethyl nipecotate (0.24-0.32 mmoles/kg). Of these ethyl nipecotate and nipecotic acid were the most effective anticonvulsants icv, but nipecotic acid was ineffective ip. Limb myoclonus and other epileptic manifestations (rearing, wild running, tonic clonic seizures) occurred in the absence of auditory stimulation after (+)-2,4-diaminobutyric acid (0.5-2.0 mumoles), (+/-)-cis-3-aminocyclohexane carboxylic acid (3.2-6.4 mumoles) and putrescine (2 mumoles). beta-Alanine (2-4 mumoles, icv) depressed respiration but did not protect against audiogenic seizures or induce myoclonus.
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PMID:Convulsant and anticonvulsant actions in DBA/2 mice of compounds blocking the reuptake of GABA. 51 Apr 1

Clonazepam (5-(2-chlorophenyl)-1,3-dihydro-7-nitro 2H-1,4 benzodiazepin-2-one) (2 mg/kg) reduced a p,p'-DDT-induced myoclonus in mice by 50%. This antimyoclonic action of clonazepam was counteracted by the serotonin (5-HT) receptor blockers methysergide, metergoline and cinnanserin and potentiated by the 5-HT uptake inhibitors fluoxetine and chlorimipramine. Clonazepam (4 mg/kg) reduced plasma tryptophan by 27%, but had no effect on brain tryptopham, 5-HT, 5-hydroxyindoleacetic acid, 5-HT synthesis and 3H-5-HT receptor binding. Clonazepam (10(-5) M) inhibited brain synaptosomal 3H-5-HT uptake by 23% and increased 3H-5-HT release by 24%. However, 2-8 mg/kg of clonazepam administered intraperitoneally had no effect on 5-HT uptake or release. gamma-Aminobutyric acid (GABA) agonists (muscimol, acetylenic GABA, amino-oxyacetic acid) and the GABA antagonists bicuculline and isoniazid had no effect on p,p'-DDT-induced myoclonus. Furthermore, bicuculline did not counteract the antimyoclonic effect of clonazepam. We suggest that the antimyoclonic action of clonazepam is mediated by enhancement of serotonergic rather than GABAergic neurotransmission.
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PMID:Antimyoclonic action of clonazepam: the role of serotonin. 52 Apr 16

The neurophysiological interactions between the high pressure neurological syndrome (HPNS) and a new beta carboline, abecarnil, were studied in the non-human primate Papio anubis. Abecarnil is a partial agonist at the benzodiazepine site on the GABA/benzodiazepine receptor. Six animals were exposed on two occasions to pressures of 91 ATA in an environment of helium and oxygen. One exposure was pretreated with a total dose of abecarnil 1.0 mg/kg, the other with an equivalent volume of vehicle. Treatment with abecarnil prevented the severe signs of HPNS occurring between 51 and 91 ATA. Onset pressures of the various signs were unaffected. Some signs, e.g. myoclonus, became more frequent when abecarnil was used. A residual protective effect of abecarnil was present 4 weeks after the dose was given, active at pressures less than 71 ATA. Changes with pressure in the EEG were recorded primarily from the frontal cortex, but were also present in the parietal and occipital areas of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the four conventional wavebands, plus two others, analysed. The most striking change was the prevention by abecarnil of the pressure-induced 100% increase in alpha wave amplitude in the frontal region. It is concluded that modulation of GABA transmission is important in controlling the expression of HPNS.
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PMID:Interactions of the beta carboline abecarnil with the high pressure neurological syndrome in a primate model. 136 51

This work focuses on the neurophysiological features in a patient with action myoclonus and mental deterioration following methylbromide intoxication. The patient is a 28-year-old man, without respiratory distress or exposure to other toxics. Myoclonus improved with polytherapy (clonazepam, 5-HT, carbidopa, GABA). The neurophysiological and neuropsychological evidence in this patient suggests a possible double site of action of methylbromide at cortical and subcortical levels.
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PMID:Methylbromide intoxication: a case report. 137 51

In Papio papio baboons benzodiazepines can facilitate the appearance of a naturally occurring non-epileptic myoclonus, suggesting a possible role of GABAergic transmission in their physiopathology. Nevertheless, as this myoclonus is blocked by physostigmine, the effect of benzodiazepines is probably due to their indirect action on the cholinergic system. Therefore, in this study, we report the effects on the non-epileptic myoclonus of drugs influencing GABAergic transmission. Systemic injections of progabide (GABA precursor), baclofen (GABAB receptor agonist) and allylglycine (glutamic acid decarboxylase inhibitor) did not modify or induce the non-epileptic myoclonus. In the same way, localized chronic injections of GABA into various cerebral structures (prefrontal and motor cortical areas, reticular magnocellular nucleus and substantia nigra) had no effect. When the two types of myoclonus were present in the same photosensitive animal, the epileptic myoclonus induced by photic stimulation was blocked by benzodiazepines but was not influenced by physostigmine, thus differing from the non-epileptic myoclonus. This suggests that different neurochemical mechanisms are involved in the two types of myoclonus, the non-epileptic myoclonus not being directly influenced by the GABAergic transmission.
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PMID:Drugs influencing the GABAergic neurotransmission have no effect on the non-epileptic myoclonus of baboons. 171 29

We describe a case of idiopathic palatal myoclonus with normal CT and NMR results, especially of the region of the inferior olive. The effective treatment with sodium valproate is reported and its relation with GABA is discussed.
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PMID:A case of idiopathic palatal myoclonus: treatment with sodium valproate. 175 67

Pretreatment with 5-hydroxytryptophan (5-HTP), a precursor of 5-HT, antagonised while pretreatment with p-chlorophenylalanine (PCPA), a 5-HT depletor, potentiated the myoclonus induced by picrotoxin, a GABA antagonist. Pretreatment with aminooxyacetic acid (AOAA), a GABA transaminase inhibitor, antagonised picrotoxin-induced myoclonus. The combined effect of the least protective doses of AOAA and 5-HTP was greater than the sum of their individual inhibitory effects on picrotoxin-induced myoclonus. Further, AOAA failed to inhibit picrotoxin-induced myoclonus in PCPA pretreated rats. These findings suggest that the central 5-HT-ergic system exerts a facilitatory influence on the GABA-ergic system and thus it is involved in the antimyoclonic action of GABA.
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PMID:A functional interaction between GABA and 5-HT in inhibiting picrotoxin-induced myoclonus in rats. 214 69

Myoclonus is a clinical term meaning a quick involuntary jerk, seen in normal subjects under certain circumstances, including sleep, and in certain disease states. It is important as a symptom that may impair function and as an indicator of neurological dysfunction. Not until patients with myoclonus and major functional disability were reported in the 1960s was attention given to understanding its basis and pharmacotherapy. Reports of myoclonus developing after anoxic brain injury, and its response to treatment with the serotonin precursor 5-hydroxytryptophan (5-HTP), drew special attention. Further experience showed that only a few patients with myoclonus benefit from 5-HTP therapy. Benzodiazepines (BDZs) are often helpful in the treatment of myoclonus. Their beneficial effects decline with chronic administration because of drug tolerance, and the theoretical basis for BDZ responses remains unclear. The relationships between myoclonus, clonus, and epilepsy are discussed, as is the possible contribution of slow signaling transmembrane receptors to synchronization of motoneuron firing, which is suggested as a hallmark of myoclonus. Myoclonus may originate in many CNS sites, but the brain-stem reticular formation is especially relevant to myoclonus. Brain-stem serotonin neurons have special influence on spinal motoneurons, on startle responses, and on myoclonus. Among 5-HT receptors, 5-HT1A receptors are related to some forms of myoclonus, although 5-HT2 receptors are also implicated. GABAA receptors are related to some forms of myoclonus. Blockade of GABAA receptors or GABA synthesis regularly evokes convulsive seizures, but administration of many GABA agonists and some GABA uptake blockers paradoxically may evoke myoclonus. Injection of GABA receptor blockers into some brain areas has anticonvulsant effects. Stimulation of GABAA receptors may therefore promote or antagonize myoclonus depending on which GABA receptors are involved, the state of the system, etc. The role of glycine receptors is well established in some animal models, but has yet to be clearly established for human myoclonus. Opiates may produce myoclonus when given intrathecally or in high dosage. The concept of excitant anesthetics and special function of certain GABA receptors is discussed.
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PMID:Myoclonus: analysis of monoamine, GABA, and other systems. 216 12


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