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 (600 mg/kg) produces myoclonic activity in mice which can be reduced by L-5-hydroxytryptophan (L-5HTP) (200 mg/kg), H75/12 (25 mg/kg), serotonin uptake blockers and two alpha-receptor blockers, phenoxybenzamine (5 mg/kg) and trazodone (5 mg/kg). Decreasing endogenous brain serotonin by pretreatment with p-chlorophenylalanine (400 mg/kg i.p.) blocked the antimyoclonic action of all of these drugs except L-5HTP. Seven other alpha-receptor blockers (phentolamine, tolazoline, yohimbine, azapetine, aceperone, nicergoline and prazosin) potentiated the antimyoclonic activity of a small dose of L-5HTP (50 mg/kg) in this animal model. We postulate that an alpha noradrenergic inhibitory synapse may be located in the neural circuit connecting a serotonergic neuron to the final motor response (p,p'-DDT-induced myoclonus).
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PMID:DDT-induced myoclonus: serotonin and alpha noradrenergic interaction. 3 58

The response of myoclonus to oral and intravenous L-5-hydroxytryptophan (5-H.T.P.) in combination with a peripheral decarboxylase inhibitor (carbidopa) and to clonazepam has been examined in 9 patients. Moderate improvement or complete cessation of myoclonus followed treatment with one or both of these regimens in 5 patients, 1 of whom also responded to the concurrent administration of L-tryptophan and a monoamineoxidase inhibitor. The remaining 4 patients were at best only slightly improved by either 5-H.T.P. or clonazepam. The responsive group consisted of 3 patients with a history of anoxia, 1 patient with non-history of severe head injury, and 1 patient with non-progressive focal myoclonus and epilepsy. This group had low levels of 5-hydroxyindole acetic acid in the lumbar cerebrospinal fluid. It is suggested that 5-H.T.P. plus carbidopa, L-tryptophan plus a monoamine-oxidase inhibitor, and clonazepam may all act by elevating brain levels of serotonin (5-H.T.) and that some human myoclonic syndromes may be specifically related to a cerebral deficiency of 5-H.T.
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PMID:Manipulation of brain serotonin in the treatment of myoclonus. 5 Dec 40

Post-hypoxic intention myoclonus is a specific myoclonic syndrome in which central serotonergic tone may be deficient. Tryptophan and 5-hydroxytryptophan administration to patients with post-hypoxic intention myoclonus increases pre-existing low levels of 5-hydroxyindoleacetic acid levels in the cerebrospinal bluid, and also suppresses myoclonus. Serotonin precursor administration does not help all patients with myoclonus and may actually worsen some myoclonic syndromes, including those secondary to lipid storage diseases. Treatments that alter serotonin metabolism can also produce myoclonus in experimental animals but their relevance to myoclonic syndromes in humans remains uncertain.
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PMID:Serotonergic mechanisms in myoclonus. 29 Jul 59

A patient with post-hypoxic myoclonus, sensitive to therapy with 5-hydroxytryptophan and clonazepam, was subjected to detailed electrophysiological investigation. Brief generalised jerks followed the critical stimulus of muscle stretch. The electroencephalogram showed generalised spikes that were associated with, but not time locked to, the myoclonus. The cranial nerve nuclei were activated upward. Analysis of the findings suggests that the mechanism of the myoclonus is hyperactivity of a reflex mediated in the reticular formation of the medulla oblongata.
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PMID:Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus. 30 26

5-Hydroxytryptophan (5-HTP) induces a characteristic behavioural syndrome of altered motor activity with muscle jerking in guinea pigs. Myoclonic jerking occurs synchronously in forelimbs and hindlimbs and is associated with a stereotyped electromyographic (EMG) pattern of a burst of activity lasting 40-50 msec in active muscles, followed by silence lasting 50-70 msec, followed by a further variable period of muscle activity. Such myoclonus may be induced also by the administration of L-tryptophan plus a monamine oxidase inhibitor (MAOI), or by agents acting as serotonin (5-HT) receptor agonists. The 5-HTP-induced syndrome is antagonised by a central decarboxylase inhibitor (NSD-1035) and by agents which block 5-HT receptors (methysergide and cyproheptadine). 5-HTP-induced jerking is abolished below the level of a spinal cord transection, but persists in decerebrate animals. No electroencephalographic (EEG) changes are seen preceding the muscle jerks. The clinical significance of this animal model of myoclonus is discussed.
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PMID:5-hydroxytryptophan-induced myoclonus in guinea pigs. A physiological and pharmacological investigations. 30 85

Post-hypoxic intention myoclonus successfully treated by long-term administration of the combination of 5-hydroxytryptophan and carbidopa is described. Persistent euphoria and diarrhoea were essential side effects. Methysergide (12 mg/day) blocked the therapeutic effect, indicating a specific serotoninergic function of precursor loading with 5-hydroxytryptophan. Tryptophan (8 g/day) had no effect on the myoclonus suggesting a reduced tryptophan hydroxylase activity. Plasma concentrations of 5-hydroxytryptophan in the range of 10--30 micromoles per liter were obtained during maintenance therapy with 900 mg 5-hydroxytryptophan per day in combination with 150 mg carbidopa per day.
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PMID:Post-hypoxic intention myoclonus treated with 5-hydroxy-tryptophan and an extracerebral decarboxylase inhibitor. 30 27

5-Hydroxytryptophan has been found to be beneficial when administered alone or in combination with extracerebral aromatic amino acid decarboxylase inhibitors for therapeutic purposes in various disorders in which myoclonus is prominent. In five subjects the effect of decarboxylase inhibitors on the accumulation and elimination of 5-hydroxytryptophan in plasma was studied. The plasma concentrations of 5-hydroxytryptophan were increased about ten fold by pretreatment with the decarboxylase inhibitors, carbidopa and benserazide. Half-lives of 2.2--3.0 hrs. were obtained following oral administration of a single dose of 5-hydroxytryptophan with or without pretreatment. In one subject the half-life of 5-hydroxytryptophan in plasma increased to 5.5 hrs. during long-term treatment with carbidopa.
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PMID:The effects of aromatic amino acid decarboxylase inhibitors on plasma concentrations of 5-hydroxytryptophan in man. 30 71

Intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) following treatment with desmethylimipramine induced development of behavioral supersensitivity to the intraperitoneally administered serotonin precursor 5-hydroxytryptophan (5-HTP) in the mouse. This behavioral syndrome, characterized by tremor and muscle twitches (myoclonus), showed a clear dose-response relationship with 5,7-DHT as well as with 5-HTP. Mice lesioned with a low dose of 5,7-DHT (20 micrograms) or a placebo were treated repeatedly with a protein synthesis inhibitor, sycloheximide (45 mg/kg, s.c., every 12 h for up to 10 days). This treatment resulted in a reversible decrease of cerebral protein synthesis varying between 70 and 20% with time between treatments. The myoclonic response to 5-HTP in animals pretreated with 5,7-DHT and by cycloheximide showed a decrease in intensity within 24 h when evaluated quantitatively by an electronic activity monitor, the results of which were confirmed by direct observation. Cycloheximide also exerted a similar, though smaller, effect following full development of sensitivity to 5-HTP over 10 days. These effects may de mediated by inhibition of rapidly turning over serotonin receptor proteins, although their interpretation is somewhat obscured by possible toxic effects of cycloheximide.
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PMID:Inhibition of 5,7-dihydroxytryptamine-induced supersensitivity to 5-hydroxytryptophan in mice by treatment with cycloheximide. 31 Mar 31

Since the advent of intensive care units the number of cases of posthypoxic action or intention myoclonus has greatly increased. This has given rise to renewed research into the physiopathology and therapy of the disease. The latent effective treatment is based on derivatives of benzodiazepine, and especially L-5-hydroxytryptophan, administered with or without an inhibitor of peripheral decarboxylase. The disadvantages of these compounds, associated with their secondary effects, make our fortuitous discovery of the effectively curative action of piracetam doubly valuable.
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PMID:[Therapeutic effect of piracetam in a case of posthypoxic action myoclonus (author's transl)]. 34 25

We evaluated the therapeutic effect of L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin (5-hydroxytryptamine), combined with carbidopa, a peripheral decarboxylase inhibitor, in patients with intention myoclonus and examined the serotonin metabolites in spinal fluid, blood and urine before and during therapy. In 18 patients with intention myoclonus due to anoxia or other brain damage, 11 derived more than 50% overall improvement during treatment with L-5HTP and carbidopa. Spinal-fluid 5-hydroxyindoleacetic acid was 35% lower in patients with intention myoclonus than in controls (P less than 0.05). Therapy with L-5HTP and carbidopa increased the concentration of serotonin metabolites in urine and spinal fluid. We postulate that a deficiency of brain serotonin is causally related to intention myoclonus and that the therapeutic effect of L-5HTP and carbidopa may be due to the repletion of serotonin in regions of the brain where serotoninergic neurons have degenerated.
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PMID:Long-term therapy of myoclonus and other neurologic disorders with L-5-hydroxytryptophan and carbidopa. 40 57


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