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)

Indoleamine-induced myoclonus in guinea pigs is a specific model of brainstem 5-HT function that can be used to characterize the indoleamine systems initiating myoclonus. 5-HT precursors and indole-containing 5-HT agonists induce myoclonus in guinea pigs, but piperazine-containing compounds do not. This selectivity of action correlates with the ability of 5-HT agonists to act at 5-HT-1 receptors. Further evidence for the involvement of a brainstem 5-HT receptor subpopulation in the initiation of myoclonus is shown by the differential ability of 5-HT antagonists to inhibit 5-HTP-induced myoclonus and of 5-HT reuptake blockers to potentiate threshold myoclonus. Distinct tryptamine receptors also may be involved in producing myoclonus, since indoleamine antagonists show differing potencies in inhibiting 5-HTP- and tryptamine-induced myoclonus. Tryptamine-induced myoclonus is, however, dependent on intact presynaptic 5-HT function. Biochemical studies indicate that 5-HT is primarily responsible for 5-HTP-evoked myoclonus, whereas tryptamine predominates in tryptamine-induced myoclonus. Both 5-HT and tryptamine may contribute to myoclonus produced by L-tryptophan. Indoleamine-induced myoclonus in guinea pigs may be valuable in studying the organization of brainstem indoleamine systems that may be involved in some forms of human myoclonus.
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PMID:5-HT-mediated myoclonus in the guinea pig as a model of brainstem 5-HT and tryptamine receptor action. 241 49

It has been found that PME without Lafora bodies is more common in Finland than elsewhere. The incidence is 1:20,000. The mode of inheritance is autosomal recessive. At first the children are healthy. Stimulus-sensitive myoclonic jerks and grand mal seizures appear at the age of 6 to 15 years. The EEG shows a generalized disturbance with spike-wave or polyspike-wave paroxysms which increase during photic stimulation. Myoclonic jerks incapacitate the patient. Within 5 years after the onset of the first symptoms, many patients have a disorder of gait and may become confined to bed. Sodium valproate alone or combined with clonazepam is the most effective therapy. However, the course of the disease is progressive. The mean age at death has been 24 years but appears to be increasing. The etiology and pathogenesis of PME without Lafora bodies are unknown. Increased excretion of indican has been noted, suggesting deficient intestinal absorption of L-tryptophan. A loss of Purkinje cells is the most prominent neuropathological feature. No inclusion bodies are present. Finnish PME patients are similar to the patients described by Unverricht from Estonia and by Lundborg from Sweden. Neuropathological data from these patients are not available. Clinically, these patients could form an entity with Finnish patients defined as a Baltic or Nordic type of PME. The gene is enriched in Finland, but elsewhere it is rare.
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PMID:Baltic myoclonus. 241 50

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

Posthypoxic action myoclonus is usually associated with impaired serotonin (5-HT) neurotransmission but in some patients 5-HT precursors aggravate and 5-HT blockers improve action myoclonus. We studied a 65-year-old man who presented with action myoclonus following a prolonged episode of moderate hypoxia and severe hypercarbia. The myoclonus increased with 5-hydroxytryptophan (5-HTP) 1,200 mg/day plus carbidopa 300 mg/day and sodium salt of valproic acid (SVA) 800 mg/day, and improved with 1 mg of clonazepam (CNZ) in an intravenous bolus. Biochemical analysis of the cerebrospinal fluid (CSF) prior to any drug therapy did not reveal abnormalities in the levels of homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) but 5-hydroxyindoleacetic acid (5-HIAA) levels were elevated in comparison with controls (33 versus 21 ng/ml). SVA therapy produced a moderate increase and 5-HTP plus carbidopa a threefold elevation of 5-HIAA in CSF and marked aggravation of action myoclonus. Methysergide (3 mg/day) totally suppressed myoclonus and decreased CSF 5-HIAA to undetectable levels. Methysergide also reduced CSF tryptophan to 40% of baseline levels. Discontinuation of methysergide and substitution by placebo was followed by reappearance of myoclonus. A partial and incomplete spontaneous remission of symptoms took place 7 months after the asphyxic episode. Action myoclonus and enhanced 5-HT neurotransmission may be present in patients in which acidosis reverses the effects of hypoxia on 5-HT neurotransmission.
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PMID:Clinical, biochemical, and pharmacological observation in a patient with postasphyxic myoclonus: association to serotonin hyperactivity. 245 56

The effects of some biologically active metabolites of tryptophan on the high pressure neurological syndrome (HPNS) were studied. Kynurenic acid, quinolinic acid, 5-hydroxytryptophan, kynurenine and 3-hydroxyanthranilic acid, at doses within the physiological range, were administered exogenously to rats prior to exposure to increased pressure and any effects on the tremor, myoclonus and convulsion end points of the high pressure neurological syndrome were observed. Quinolinic acid (25 and 50 mg/kg) and kynurenine (50 mg/kg) reduced the onset pressure for tremor, but not myoclonus or convulsions. Kynurenic acid (100 mg/kg) increased tremor onset pressure; 5-hydroxytryptophan (20 mg/kg) slightly increased onset pressure for tremor but decreased that for myoclonus. 3-Hydroxyanthranilic acid (20 mg/kg) had no significant effect on any of the motor signs of the syndrome. These data provide further support for the idea that the motor events seen in the high pressure neurological syndrome are not produced by a single mechanism. Differences between the responses to related metabolites suggest that the precise balance between compounds such as kynurenic acid and quinolinic acid may be important in the appearance of the high pressure neurological syndrome.
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PMID:The effects of kynurenic acid, quinolinic acid and other metabolites of tryptophan on the development of the high pressure neurological syndrome in the rat. 292 79

Although relatively few drugs that specifically influence serotonin neurons have been used in humans, a wide variety of drugs has been used to modify serotonergic function in experimental animals. Several classes of agents increase serotonergic function. These include serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) and monoamine oxidase inhibitors, which elevate serotonin stores; uptake inhibitors and releasers, which increase the concentration of serotonin in the synaptic cleft; and direct serotonin agonists, which mimic the action of serotonin on synaptic receptors. In addition, several kinds of drugs decrease serotonergic function, including serotonin depletors and agents that destroy serotonin neurons, as well as direct serotonin-receptor antagonists. The array of drugs now available improves the opportunities for clarifying the physiological roles of serotonin and gives promise of several therapeutic applications, including treatment of myoclonus.
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PMID:Biochemical pharmacology of the serotonin system. 293 68

The acute behavioural consequences of intragastric p,p'-DDT in high doses to mice are stimulus sensitive abrupt muscle jerks (myoclonus). The serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) ameliorated in contrast to the natural precursor tryptophan, the neurotoxin-induced myoclonus. The extracerebral decarboxylase inhibitor carbidopa and the selective 5-HT reuptake inhibitor paroxetine both enhanced the antimyoclonic action of 5-HTP. The effect was reversed by the 5-HT receptor blockers cinanserine and methysergide. The data add further evidence to a central serotonergic mechanism involved in p,p'-DDT induced myoclonus.
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PMID:p,p'-DDT-induced myoclonus in mice: the effect of enhanced 5-HT neurotransmission. 298 13

Administration of p,p'-DDT to rats produced myoclonus, but unlike previous studies in mice, this was not decreased by administration of clonazepam. Precursors of 5-hydroxytryptamine (5-HT) (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists, quipazine and Org 6582 did not. Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT. Drugs altering the function of dopamine and noradrenaline (apomorphine, clonidine or phenoxybenzamine) also had no effect on this myoclonus. Administration of monoamine oxidase inhibitors (MAOIs; pargyline, nialamide and tranylcypromine) markedly attenuated the myoclonus, an effect that could not be attributed to an action on any one monoamine system. No observable changes in cerebral biochemical parameters of 5-HT occurred at the onset of myoclonus, although tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in brain were increased following periods of prolonged myoclonus. Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem. Although this was similar to electrophysiological findings in some human patients with post-anoxic action myoclonus, the pharmacological studies suggest that the myoclonus induced by p,p'-DDT in the rat is not a suitable model for screening potential drugs to be used in the treatment of this disorder.
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PMID:Myoclonus in the rat induced by p,p'-DDT and the role of altered monoamine function. 402 63

Three cases are presented on patients on an MAOI who developed a transient syndrome of myoclonus, hyperreflexia, jaw quivering, teeth chattering and diaphoresis after L-Tryptophan was added. Caution is advised when considering the addition of a serotonergic agent to MAOI's.
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PMID:Myoclonus, hyperreflexia and diaphoresis in patients on phenelzine-tryptophan combination treatment. 406 40

Tryptamine (1-320 mg/kg) evoked only slight muscle jerking in naive guinea-pigs but, in animals pretreated with pargyline (75 mg/kg; 1 hr previously), tryptamine induced a dose-dependent (6-160 mg/kg) myoclonus. The myoclonus induced by tryptamine (40 mg/kg) plus pargyline (75 mg/kg) was differentially inhibited by the indoleamine receptor antagonists, methergoline (5 mg/kg) which was more potent than methysergide (10 mg/kg), mianserin (10 mg/kg) which was more potent that cyproheptadine (10 mg/kg) and propranolol (20 mg/kg) which was more potent than cinanserin (10 mg/kg). This rank order of potency differed from that observed for the order of potency of these drugs in inhibiting the myoclonus induced by L-5-hydroxytryptophan (5HTP) plus carbidopa in guinea-pigs (Luscombe, Jenner and Marsden, Neuropharmacology, 1981), perhaps indicating involvement of pharmacologically distinct indoleamine receptors. Manipulation of presynaptic function of 5-hydroxytryptamine (5HT) by tryptophan hydroxylase inhibition with p-chlorophenylalanine to produce depletion of cerebral 5HT, or by an L-tryptophan load to elevate 5HT in brain, suggested that the functional integrity of serotonergic neurones is required for the expression of myoclonus induced by tryptamine plus pargyline. A range of blockers of 5HT re-uptake did not alter the jerking produced by tryptamine (40 mg/kg) in guinea pigs pretreated with pargyline (75 mg/kg; 1 hr previously), or the threshold myoclonus induced by a smaller dose of tryptamine (10 mg/kg; plus pargyline 75 mg/kg). It is suggested that myoclonus induced by tryptamine in guinea pigs pretreated with pargyline involves activation of post-synaptic indoleamine receptors by tryptamine by a mechanism which requires intact presynaptic function of 5HT.
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PMID:Tryptamine-induced myoclonus in guinea-pigs pretreated with a monoamine oxidase inhibitor indicates pre- and post-synaptic actions of tryptamine upon central indoleamine systems. 613 Apr 89


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