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)

p,p'-DDT-induced myoclonus in mice has been proposed as a model of stimulus-sensitive action myoclonus responsive to L-5-HTP and clonazepam treatment. However, we have been unable to confirm the ability of clonazepam to reduce myoclonus induced by p,p'-DDT in the rat. A detailed pharmacological, biochemical, and physiological investigation in the latter species shows p,p'-DDT-induced myoclonus not to resemble stimulus-sensitive action myoclonus occurring in humans. Precursors of 5-HT (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists quipazine and Org 6582 did not. 5-HT antagonists (methergoline, methysergide, and cinanserin) did not potentiate myoclonus induced by p,p'-DDT. In contrast, administration of MAOIs (pargyline, nialamide, and tranylcypromine) markedly attenuated the myoclonus. No observable changes in cerebral 5-HT biochemical parameters occurred at the onset of myoclonus, although brain tryptophan and 5-HIAA were increased following periods of prolonged myoclonus. Electrophysiological analysis of p,p'-DDT-induced myoclonus in the rat revealed changes in EEG and EMG activity that were different from those observed in human reticular reflex myoclonus. In conclusion, in contrast to the mouse, myoclonus induced by p,p'-DDT in the rat does not appear to be a suitable model of 5-HT-sensitive action myoclonus in man.
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PMID:p,p'-DDT-induced myoclonus in the rat and its application as an animal model of 5-HT-sensitive action myoclonus. 241 51

Clonazepam is a potent anticonvulsant 1,4-benzodiazepine that controls some types of myoclonus. Its primary mode of action is to facilitate GABAergic transmission in the brain by a direct effect on benzodiazepine receptors. GABA receptors lie on the cell bodies of dorsal raphe neurons, and GABA acts to inhibit raphe cell firing, an action potentiated by benzodiazepines. Clonazepam does not alter 5-HT synthesis but decreases 5-HT utilization in brain and blocks the egress of 5-HIAA from the brain. It is not known whether the actions of clonazepam in altering 5-HT function are responsible for its antimyoclonic action, since these are observed only after large doses. Also, the effects of clonazepam are the exact opposite of those predicted from the beneficial effects of 5-HTP in human myoclonic disorders. Finally, why clonazepam, more than other benzodiazepines, is of benefit in the treatment of myoclonus is not clear. This may be due to some pharmacokinetic feature of the drug in conjunction with its potency at benzodiazepine receptors.
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PMID:Mechanism of action of clonazepam in myoclonus in relation to effects on GABA and 5-HT. 241 52

A deficiency of dihydrobiopterin synthesis was found in a 27-year-old man with mild mental retardation, rigid spasticity, hyperreflexia, dystonia, myoclonus, and delay in the initiation of action, since age 10. Symptoms improved after sleep. Urine contained large amounts of neopterin and a trace of biopterin. Dihydropteridine reductase activity in red blood cells was normal. CSF levels of HVA and 5-HIAA were low. Tetrahydrobiopterin administration lowered serum phenylalanine and improved the symptoms.
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PMID:Dihydrobiopterin synthesis defect: an adult with diurnal fluctuation of symptoms. 243 82

Monoamine metabolites, biopterin, acetylcholinesterase (AChE) activity, and somatostatin-like immunoreactivity (SLI) were determined in the lumbar cerebrospinal fluid (CSF) of 24 patients with dementia of the Alzheimer type (DAT) without myoclonus or extrapyramidal signs, in 8 patients with DAT and myoclonus, and in 14 age-matched healthy control subjects. In patients with DAT with myoclonus as compared with both DAT patients without myoclonus and control subjects, the concentrations of homovanillic acid and biopterin were significantly decreased. 5-Hydroxyindoleacetic acid was significantly lower in patients with myoclonic DAT as compared to patients with nonmyoclonic DAT, but not significantly lower than in control subjects. CSF AChE and SLI were significantly reduced in patients with DAT with or without myoclonus, as compared with control subjects, but AChE and SLI were not significantly different between dementia groups. These results suggest that DAT patients with myoclonus represent a distinct clinical and neurochemical DAT subtype.
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PMID:Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease. 246 3

Milacemide, a glycine prodrug that is able to enter the brain readily, has been shown to have an antimyoclonic property in the p,p'-DDT-induced myoclonus syndrome. Milacemide increased regional 5-HT and dopamine and decreased 5-HIAA, DOPAC and HVA levels in naive rats. In p,p'-DDT-treated rats, 5-HT levels were unchanged at the time the rats experienced spontaneous myoclonus in all brain regions except in the striatum, where it increased. 5-HIAA levels increased but did not reach significant levels except in the striatum. Dopamine, DOPAC, HVA and norepinephrine were unchanged. When rats were treated concurrently with both p,p'-DDT and milacemide, regional 5-HT levels were increased and NE levels in the brainstem and cerebellum decreased. Depletion of brain serotonin by pretreatment with PCPA or with 5,7-DHT, or blocking 5-HT receptors with different 5-HT antagonists, failed to eliminate the antimyoclonic property of milacemide. This antimyoclonic effect of milacemide may be mediated through other mechanisms besides its ability to increase brain 5-HT levels. Possible mechanisms to be considered are its antiepileptic property, and its ability to increase brain glycine levels. Milacemide may have potential for therapeutic trials in patients with myoclonus.
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PMID:Milacemide increases 5-hydroxytryptamine and dopamine levels in rat brain--possible mechanisms of milacemide antimyoclonic property in the p,p'-DDT-induced myoclonus. 257 9

Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5-HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences.
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PMID:Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5-hydroxytryptophan in the rat. 258 10

The possibility of disturbed dopamine and serotonin metabolism in the progressive myoclonus epilepsy (PME) occurring in Finland (a type of PME without Lafora bodies) was examined. Both basal concentrations of HVA and 5-HIAA in the CSF and their increase after oral probenecid administration were studied in 19 PME patients and in 19 age- and sex-matched control patients. The control patients had grand mal epilepsy but not myoclonus or ataxia. The basal value of HVA was significantly reduced and that of 5-HIAA was also slightly reduced in the PME patients as compared to the values of the epileptic controls or to those of 26 nonepileptic controls. The concentrations of HVA and 5-HIAA also seemed to correlate with the severity of the PME. The most severely affected patients had generally the lowest values. After oral probenecid this trend was also seen when the increases of HVA and 5-HIAA were expressed per microgram CSF probenecid, i.e. the mildly affected PME group showed higher increases in response to probenecid than the most severely affected PME group. The PME patients had higher probenecid levels in the CSF than the epileptic controls.
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PMID:Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with progressive myoclonus epilepsy. 616 2

Eleven patients with long-standing progressive myoclonus epilepsy, PME, and age- and sex-matched epileptic controls received L-tryptophan (L-Trp) 100 mg/kg body weight combined with carbidopa in addition to their usual anticonvulsant regimen. During six weeks of the trial an improvement in activities of daily living and a decrease of action myoclonus was noted in the PME patients. The frequency of seizures compared with the past year decreased significantly in the PME patients, but not in the epileptic controls. Changes in the EEGs of the PME patients were scant, but a slight decrease was noted in myoclonic spikes. Both plasma Trp and platelet 5-HT increased significantly and at least as much as in epileptic controls. 5-HIAA and HVA concentrations in the CSF of the PME patients increased significantly during the trial. The results support previous findings concerning Trp treatment in PME, and longer trials with Trp + carbidopa could be of value in this disease.
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PMID:L-tryptophan-carbidopa trial in patients with long-standing progressive myoclonus epilepsy. 617 51

To study the purported role of central monoamine disturbances in the pathophysiology of the opsoclonus-myoclonus syndrome, the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid were measured in cerebrospinal fluid samples from 27 affected children and 47 age- and gender-matched control subjects by high-pressure liquid chromatography with electrochemical detection. 5-Hydroxyindoleacetic acid and homovanillic acid concentrations in the cerebrospinal fluid were approximately 30 to 40% lower in opsoclonus-myoclonus patients compared to control subjects, and the normal inverse correlation between age and monoamine metabolite concentrations in the cerebrospinal fluid of control subjects was not found in opsoclonus-myoclonus patients. Patients with the lowest values were less than 4 years old, and a subgroup had extremely low levels, but differences in older children were not significant. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus-myoclonus patients. None of the patients exhibited high levels of monoamine metabolites. Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patients receiving corticotropin or steroids at the time of lumbar puncture. Clinical variables that could be excluded were paraneoplastic etiology, anesthetic for lumbar puncture, syndrome duration, age at onset, gender, response to steroids, length of time until initiation of corticotropin or steroids, presence of seizures, opsoclonus, and functional impairment. These data suggest a disturbance and possible altered ontogeny of serotonin or dopamine neurotransmission in a subpopulation of children with opsoclonus-myoclonus with low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in the pediatric opsoclonus-myoclonus syndrome. 753 17

We have previously reported the presence of posthypoxic, audiogenic myoclonus in rats after cardiac arrest and the ability of the 5-HT precursor, 5-HTP, to attenuate these muscle jerks. In addition, we have recently shown that 5-HT2 and 5-HT3 agonists can reduce the severity of myoclonus in these animals, suggesting a deficiency in serotonergic neurotransmission. In the present study, the levels of 5-HTP, 5-HT, and 5-HIAA were measured in seven regions of the brain in myoclonic and normal rats to identify the areas of the brain in which a serotonergic dysfunction resides. Similar to previous studies, we observed pronounced posthypoxic, audiogenic myoclonus 3 and 14 days after resuscitation from cardiac arrest, with a resolution of the abnormal movements by 45 days postarrest. HPLC measurements revealed significant changes in indole levels in the following areas of the brain: cortical 5-HIAA, striatal 5-HT, striatal 5-HIAA, hippocampal 5-HT, mesencephalic 5-HIAA, myelencephalic 5-HT, myelencephalic 5-HIAA, cerebellar 5-HTP, and cerebellar 5-HT. The changes in striatal 5-HT, cortical 5-HIAA, and mesencephalic 5-HIAA appear most relevant to the pathophysiology of posthypoxic myoclonus because regression analyses showed significant correlations between the myoclonus scores of the animals and the levels of these indoles. Based on the observed pattern of results, we postulate a dysfunction in serotonergic lateral (cortical) and far lateral (extrapyramidal) ascending pathways in posthypoxic myoclonus.
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PMID:Association between brain indole levels and severity of posthypoxic myoclonus in rats. 754 90


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