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)

Locomotor activity and hole-board exploration (frequency and time spent head-dipping) were impaired in male rats by injecting IP the 5-HT agonists, fluoxetine and 5-HTP. This treatment produced also myoclonus and increased the time spent resting during trials. The chronic ingestion of chlorimipramine (CIM) or the injection of the 5-HT receptor blocker, methysergide (15 mg/kg) prevented the action of the 5-HT agonists on locomotion and resting and blocked the appearance of myoclonus. Both CIM and methysergide prevented to a minor degree the fluoxetine-5-HTP-induced decrease of exploration. The chronic ingestion of CIM clearly potentiated the effects of methysergide on hole-board exploration. Results suggest that the chronic treatment with therapeutic doses of CIM reduces the functional activity of some 5-HT systems in the brain of the rat, probably by blockade of post-synaptic 5-HT receptors. This does not preclude, however, that CIM may also alter some NA systems.
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PMID:Effects of the chronic ingestion of therapeutic doses of chlorimipramine on the behavioral action of agonists and antagonists of serotonin in male rats. 660 38

L-5-hydroxytryptophan (L-5-HTP)-induced myoclonus was used as a behavioral index of central serotonergic activity. Estradiol benzoate (EB) and progesterone (P) influenced the induction of myoclonus by L-5-HTP. When L-5-HTP was injected 46 h after EB, myoclonus was enhanced. P blocked this effect on EB when 100 or 125 mg/kg L-5-HTP (but not 80 mg/kg) was given 6 h after P in EB-primed animals. When L-5-HTP was given 3 or 11-15 h after P in EB-primed animals, there was no inhibitory effect of P on myoclonus. In fact, at the lowest dose (80 mg/kg), L-5-HTP increased myoclonus when given 3 h after P in EB-primed animals. The inhibitory effects of P in EB-primed females on myoclonus were temporally correlated with the display of lordosis, suggesting that the neural progestin receptor mechanisms that have been proposed to mediate P effects on lordosis are also involved in the inhibitory effects of P on myoclonus.
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PMID:Estradiol and progesterone influence a serotonin mediated behavioral syndrome (myoclonus) in female guinea pigs: comparison with steroid effects on reproductive behavior. 660 96

A 22 year old patient with non-familial progressive myoclonus, macular cherry-red spot, moderate cerebellar syndrome and normal intelligence is described. The myoclonus began at the age of 18 years. Focal myoclonus could easily be elicited by voluntary and passive movements, and by touch and electrical stimulation of median nerve. Somatosensory evoked potentials showed a high voltage early component. Jerk-locked averaging of the EEG preceding action myoclonus detected an otherwise hidden, time-related, EEG spike. The myoclonus responded partially but clearly to L-5 hydroxytryptophan plus carbidopa treatment. Biochemical study showed an alpha-neuraminidase deficiency in cultured fibroblasts: the decrease in this enzyme activity was compared to that found in a patient affected by mucolipidosis III.
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PMID:Cherry-red spot myoclonus syndrome and alpha-neuraminidase deficiency: neurophysiological, pharmacological and biochemical study in an adult. 677 61

Six patients with myoclonus of varying cause were treated with L-5-hydroxytryptophan (L-5-HTP) and carbidopa. While spontaneous myoclonus decreased in three of the patients and action myoclonus in four, only two patients had marked functional improvement. Side effects included gastrointestinal and affective disturbances. L-5-HTP therapy caused a diminished frequency of paroxysmal discharges in the electroencephalograms of three patients which did not always correlate with clinical improvement. Lumbar cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration after probenecid was decreased in all patients prior to therapy, but this reduction did not predict treatment response. Urinary excretion patterns for 5-HTP, serotonin, and 5-HIAA during treatment were similar in responders and nonresponders. It is concluded that while some patients with myoclonus do benefit from L-5-HTP therapy, biochemical and electrophysiological tests are not useful predictors of treatment response, and the high incidence of side effects limits the usefulness of this therapy.
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PMID:Treatment of myoclonus with L-5-hydroxytryptophan and carbidopa: clinical, electrophysiological, and biochemical observations. 696 54

Myoclonus was induced in guinea pigs in a dose-dependent manner by intraperitoneal injection of L-5-hydroxytryptophan (L-5-HTP). At a dosage of 400 mg per kilogram, all animals developed myoclonus. Autoradiographic analysis, using the [14C]-deoxyglucose method, showed increased glucose utilization in the ventral and ventral anterior thalamic nuclei and decreased glucose utilization in the cortex and molecular layer of the hippocampus. These changes were dose-dependent and occurred to a lesser extent in both myoclonic and non-myoclonic guinea pigs given an ED50 of L-5-HTP, demonstrating that the autoradiographic changes are not dependent on the presence of myoclonus. We believe that the thalamus is the final common pathway for the expression of myoclonus induced by L-5-HTP.
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PMID:Functional anatomy of L-5-hydroxytryptophan-induced myoclonus in the guinea pig. 697 11

The effect of chronic cortisol administration (12.5 mg/kg per day p.o.) was studied in guinea pigs using two behavioral models; apomorphine-induced stereotypy (SB) and 1-5-HTP-induced myoclonus (MJB). Diurnal variations in behavioral sensitivity were evaluated by behavioral testing at five time points over a 24 h period at bi-weekly intervals. Cortisol succinate administration suppresses 1-5-HTP myoclonus in all animals and abolishes diurnal fluctuations in sensitivity during the first two weeks of therapy. At four weeks, a subgroup is observed which is behaviorally hypersensitive to 1-5-HTP. These changes occur in association with a reduction in the behavioral response to apomorphine but in the absence of major disruption in diurnal behavioral threshold variation to apomorphine. Chronic cortisol administration appears to induce major alterations in central serotonin-mediated behaviors. This observation may explain the therapeutic effect of corticosteroids in certain forms of myoclonus and the role of cortisol rhythm disturbances in the context of a variety of psychiatric disorders.
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PMID:Modification of central serotonergic and dopaminergic behaviors in the course of chronic corticosteroid administration. 697 54

A scleroderma-like illness developed in a patient treated with L-5 hydroxytryptophan (L-5HTP) and carbidopa for intention myoclonus. The patient had high plasma kynurenine levels that remained high when the L-5HTP-carbidopa combination was discontinued, However, levels rose futher on drug rechallenge, suggesting that the drug unmasked an abnormality in one of the enzymes that catabolize kynurenine. Plasma kynurenine was also determined to be high in seven of 15 patients wth idiopathic scleroderma, but not in eight patients with intention myoclonus treated with L-5HTP and a decarboxylase inhibitor and in whom scleroderma did not develop or in 10 patients with Parkinson's disease treated wth L-dopa and carbidopa. Our data and studies in the literature suggest that two factors may be important in the pathogenesis of some scleroderma-like illness: high plasma serotonin and the abnormality associated with elevated kynurenine.
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PMID:Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. 699 35

L-5-Hydroxytryptophan (5HTP) induces in guinea pigs a myoclonic jerking which is dependent upon stimulation of brainstem 5-hydroxytryptamine (5HT) receptors. We have investigated the ability of 5HT precursors and a range of synthetic 5HT agonists to produce myoclonus. The 5HT precursors and 5HT agonists containing an indole nucleus induced dose-dependent jerking in guinea pigs. In contrast, 5HT agonists possessing a piperazine moiety induced occasional jerking only at toxic doses, but not a those doses normally associated with 5HT agonist activity. The difference in activity between the indole-containing compounds and piperazine-containing 5HT agonists suggests that myoclonus is due to activation of an indole-selective brainstem 5HT receptor and provides further evidence for multiple cerebral 5HT receptors.
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PMID:Myoclonus in guniea pigs is induced by indole-containing but not piperazine-containing 5HT agonists. 708 78

Possible involvement of prostaglandins (PG) in the antimyoclonic action of clonazepam was examined in the p,p'-DDT-animal model of myoclonus. PG synthesis inhibitors and the PG antagonist polyphloretin phosphate (PPP) counteracted the antimyoclonic action of clonazepam in mice. PGE2 reduced DDT-induced myoclonus; this effect was blocked by PPP. Another antimyoclonic drug combination, L-5-hydroxytryptophan plus chlorimipramine, was not blocked by PPP or indomethacin. The antimyoclonic action of clonazepam may be mediated by enhancement of PG synthesis.
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PMID:Role of prostaglandins in the antimyoclonic action of clonazepam. 723 84

The effects of 3-acetylpyridine (3-AP), which destroys the inferior olive, and harmaline, which stimulates inferior olive-climbing fiber activity, on DDT-induced myoclonus, wee studied in rats. 3-AP shortened and harmaline delayed the time of onset of myoclonus after intragastric administration of DDT. 3-AP also counteracted the antimyoclonic action of L-5-hydroxytryptophan plus chlorimipramine, clonazepam and phenoxybenzamine in this animal model. The results suggest that these antimyoclonic agents require an intact olivocerebellar pathway for their action.
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PMID:Relationship of inferior olive-climbing fibers to p,p'-DDT-induced myoclonus in rats. 726 34


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