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)

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

A myoclonic syndrome consisting of tremor, myoclonus, and seizures was produced following the systemic administration of 5-hydroxytryptophan to adult rats previously given intracisternal injections of 5,7-dihydroxytryptamine and systemic desmethylimipramine, but not in their controls. This behavioral response was blocked by pretreatment with the putative serotonin receptor blocking agents methysergide, lysergic acid diethylamide, and bromolysergic and diethylamide, as well as centrally effective doses of the aromatic amino acid decarboxylase inhibitor Ro4-4602. Blockers of receptors of other neurotransmitters had little effect. This neurologic response in the adult rat may be relevant to some forms of clinical myoclonus and may be useful in testing potential agonists and antagonists of serotonin receptors in the mammalian central nervous system.
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PMID:Myoclonus after 5-hydroxytryptophan in rats with lesions of indoleamine neurons in the central nervous system. 108 96

The capacity of the putative S2 serotonin receptor antagonists, pirenperone, pipamperone, ketanserin and cinanserin, to block the myoclonic syndrome produced by 30 mg/kg of L-5-hydroxytryptophan (5-HTP) [after lesioning 5-hydroxytryptamine (serotonin, 5-HT)-containing neurons with 5,7-dihydroxytryptamine (DHT)] or 15 mg/kg of fenfluramine (FF) or p-chloroamphetamine (PCA) was tested in adult male Sprague-Dawley rats. S2 antagonists inhibited limb (arrhythmic and asynchronous) and axial (truncal) myoclonus in a dose-dependent manner in the rank order of potency: pirenperone greater than pipamperone greater than ketanserin = cinanserin. Abnormal movements (myoclonus, lateral head weaving) of the myoclonic syndromes were better antagonized than postural abnormalities (hindlimb abduction, hunching of back). Centrally acting drugs, selective for S2 receptors (pirenperone, pipamperone), exhibited greater antimyoclonic properties than the non-selective 5-HT antagonist methysergide, which was as effective as ketanserin and cinanserin. Significant non-specific reduction in myoclonus without the improvement of other behavioral responses followed treatment with sedative/neuroleptic drugs, such as haloperidol (but not the non-neuroleptic dopamine antagonist sulpiride), clonazepam and diazepam. The anticonvulsants valproic acid (100 and 300 mg/kg), adrenocorticotrophic hormone (ACTH; 100 and 300 U/kg), diphenylhydantoin (15 mg/kg), and phenobarbital (20 mg/kg) and drugs which do not act principally at S2 receptors were ineffective in these models. These data support the hypothesis that myoclonus in behavioral models induced by 5-HT is S2 receptor mediated. S2 antagonists could have a role in the treatment of human myoclonus.
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PMID:Antimyoclonic properties of S2 serotonin receptor antagonists in the rat. 293 77

The development of direct serotonin agonists, selective inhibitors of serotonin uptake, serotonin receptor antagonists, and other drugs affecting serotonergic function has aided the study of physiologic functions of brain serotonin neurons in laboratory animals and the recognition and classification of serotonin receptor subtypes. Agents of these types are real or potential drugs for the treatment of psychiatric disorders (e.g., depression) and other disorders such as overeating, alcoholism, myoclonus, and chronic pain. In addition, the agents may permit assessment of the functional state of brain serotonin receptors in humans.
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PMID:Pharmacologic modification of serotonergic function: drugs for the study and treatment of psychiatric and other disorders. 351 85

In male Swiss mice, muscimol produced myoclonic jerks. A 3 mg/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain serotonin levels by the administration of 5-hydroxytryptophan (80-160 mg/kg) in combination with a peripheral decarboxylase inhibitor resulted in an inhibition of the muscimol effect. However, in a similar experiment l-dopa (80-160 mg/kg) was without effect. In doses of 3-10 mg/kg, the serotonin receptor agonist MK-212 caused a dose-dependent blockade of the response of muscimol. Of the benzodiazepines, clonazepam (0.1-0.3 mg/kg) was found to be several fold more potent than diazepam (0.3-3 mg/kg) in blocking the myoclonic jerks. While (-)-baclofen (1-3 mg/kg) proved to be an effective antagonist of muscimol, its (+)-isomer (5-20 mg/kg) lacked this property. Considering the fact that 5-HTP and the benzodiazepines have been found to be beneficial in the management of clinical myoclonus, the muscimol-induced myoclonus seems to be a satisfactory animal model that may prove useful for the development of new drug treatments for this condition. Our present study indicated the possible value of MK-212 and (-)-baclofen in the management of clinical myoclonus.
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PMID:Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice. 611 80

Since p,p'-DDT-induced myoclonus is ameliorated by serotonin agonists and aggravated by serotonin antagonists, the effect of p,p'-DDT on serotonin metabolism in rat brain was examined. p,p'-DDT (600 mg/kg intragastrically) elevated plasma tryptophan as well as tryptophan and 5-hydroxyindoleacetic acid concentrations in all seven regional areas of the brain assayed. Serotonin levels were elevated only in the midbrain and cerebellum of p,p'-DDT-treated rats. p,p'-DDT increased serotonin turnover in the medulla and midbrain. p,p'-DDT had no effect on the transport of 5-hydroxyindoleacetic acid out of the central nervous system, serotonin uptake and release from nerve terminals, or serotonin receptor binding in the brain. The findings in this study do not support a brain serotonin deficiency hypothesis as the explanation for the response of p,p'-DDT-induced myoclonus to serotonin agonists.
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PMID:p,p'-DDT-induced alterations in brain serotonin metabolism. 617 20

This is a critical review of the serotonin hypothesis of myoclonus for the purpose of identifying new pharmacologic therapies. The literature on myoclonus and serotonin neuropharmacology reveals evidence for serotonergic abnormalities in some human myoclonic disorders, new serotonin receptor subtypes and data on their molecular structure and function, more selective drugs, and experimental evidence linking certain serotonin receptor subtypes with myoclonus. This article provides an overview of clinical experience with serotonergic drugs, new investigational drugs, and strategies for gathering data critical to linking particular receptor abnormalities and drugs with specific human myoclonic disorders. Such information will allow the use of receptor subtype-selective agonists and antagonists for the treatment of myoclonus.
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PMID:Serotonin and human myoclonus. Rationale for the use of serotonin receptor agonists and antagonists. 751 28

Serotonin syndrome, a condition with numerous clinical neurological manifestations, is the result of central serotonergic hyperstimulation. Features of the syndrome include mental status and behavioral changes (agitation, excitement, hypomania, obtundation), motor system involvement (myoclonus, hemiballismus, tremor, hyperreflexia, motor weakness, dysarthria, ataxia) and autonomic symptoms (fever, chills, diarrhea). Serotonin syndrome has been reported exclusively in patients on medications for psychiatric illness and Parkinsonism, despite the fact that the putative action of many antimigraine agents also involves the serotonin system. We herein report six patients with migraine who developed symptoms suggestive of the serotonin syndrome. Five were taking one or more serotomimetic agents for migraine prophylaxis (sertraline, paroxetine, lithium, imipramine, amitriptyline). In each case the symptoms and signs developed in close temporal proximity with use of a migraine abortive agent known to interact with serotonin receptors. In three instances the agent was subcutaneous sumatriptan and, in three, intravenous dihydroergotamine. In each instance the symptoms were transient and there was full recovery. With the ever increasing use of migraine medications active at serotonin receptor sites, cases of serotonin syndrome will likely occur more frequently. It is important that physicians treating migraine are aware of the serotonin syndrome and are able to recognize its varying presentations.
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PMID:Serotonin syndrome complicating migraine pharmacotherapy. 886 67

We present the case of a 35-year-old woman who developed serotonin syndrome after receiving a single dose of the cyclic antidepressant imipramine (Tofranil). She was already being treated for depression with paroxetine (Paxil), a selective serotonin reuptake inhibitor. Two hours after receiving imipramine, the patient developed tachycardia, delirium, bizarre movements, and myoclonus, all classic findings of serotonin syndrome. Her antidepressants were discontinued and she was treated with intravenous fluids, sedation, and a short course of cyproheptadine, a serotonin receptor antagonist. All symptoms resolved completely within 24 hours. In this case report, we review the drug interactions that can precipitate serotonin syndrome, and give recommendations for the diagnosis and treatment of this potentially fatal disorder.
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PMID:Serotonin syndrome: case report and review of the literature. 941 60

The serotonin syndrome is the result of excess stimulation of central nervous 5-hydroxytryptamine (5HT)-1a and 5HT-2 receptors. The diagnosis requires a history of exposure to agents active at serotonin receptors and the presence of alterations in mental status, autonomic instability, and neuromuscular abnormalities such as tremor, hyperreflexia, or myoclonus. In this descriptive case series, five cases of serotonin syndrome are reported. All patients gave a history of recent exposure to one or more serotonergic medications, including moclobemide, paroxetine, sertraline, and venlafaxine, with clinical evidence of serotonin syndrome. All patients were administered cyproheptadine (4-8 mg orally) for serotonergic signs. Three had complete resolution of signs within 2 h of administration. Another two had a residual tremor or hyperreflexia following the first dose, which resolved following a repeat dose. There were no adverse outcomes from cyproheptadine use. The role of specific serotonin receptor antagonists such as cyproheptadine in the treatment of the serotonin syndrome remains to be delineated. Its use should be considered an adjunct to supportive care. Currently, it is unknown whether cyproheptadine modifies patient outcome.
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PMID:Treatment of the serotonin syndrome with cyproheptadine. 2714 91


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