Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In guinea pigs, myoclonus can be induced by 5-hydroxytryptamine (5-HT, serotonin) precursors and synthetic 5-HT receptor agonists, yet the receptor subtype specificity of this behavior is not fully delineated. Guinea pigs were pre-treated with carbidopa (50 mg) followed by one of eight 5-HT antagonists: (-)-N-tert-butyl-3-[4-(2-methoxyphenyl) piperazin-1-yl]-2-phenyl propionamide ((-)-WAY 100135) (5-HT1A), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridyl)-cy clohexancarboxamide (WAY 100635) (5-HT1A), methiothepin mesylate (5-HT1/2), mesulergine hydrochloride (5-HT2A/2C), N[4-methoxy-3-(4-methyl-L-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2 ,4-oxadizol-3-yl) (GR 127935) (5-HT1D), trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-fluorop hen yl) propen-1-yl]phenol, hemifumarate (SR 46349) (5-HT2), ondansetron hydrochloride (5-HT3), and [1-[2-[methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-meth oxy-1H-indole-3-carboxylate (GR 125487) (5-HT4). Thirty minutes later, they received 5-hydroxytryptophan (5-HTP) (75 mg/kg, sc) and myoclonic jumping rates were assessed every 10 min for 200 min by a blinded observer. Repeated measures analysis of variance of drug-induced antagonism of 5-HTP-induced myoclonus revealed a significant effect for the 5-HT receptor antagonists methiothepin mesylate, GR127935, and mesulergine hydrochloride compared to placebo, and each of these drugs inhibited 5-HTP-induced myoclonus in a dose-dependent fashion. Based on the receptor profiles of the three effective antagonists, 5-HTP-induced myoclonus is influenced by the 5-HT1/2 receptor systems. The absence of a significant change with any other receptor subtype antagonist suggests that myoclonus is not related to diffuse activation of central serotonergic mechanisms.
 ...
PMID:5-Hydroxytryptophan-induced myoclonus in guinea pigs: mediation through 5-HT1/2 receptor subtypes. 965 Aug 47

The present study examined the role of 5-hydroxytryptamine 5-HT receptor subtypes on 5-hydroxytryptamine- (5-HT-) mediated myoclonus in guinea pigs, evaluating head and whole-body jerking as two distinct behavioural responses. Myoclonus was induced by the 5-HT precursor L-5-hydroxytryptophan (L-5-HTP) and the non-selective 5-HT1A/1B/5-HT2 receptor agonist 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT). The selective 5-HT1A receptor antagonist WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cycloh exanecarboxamide trihydrochloride) inhibited both head and whole-body jerking. The selective 5-HT1B/1D receptor antagonist GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxamide hemifumarate) only inhibited whole-body jerking, which resulted in unmasked head jerking. Co-administration of GR127935 and the selective 5-HT2A receptor antagonist MDL100.151 ((+/-)-alpha-(2,3-dimethoxyphenyl)-1-[-2-(4-fluorphenyl)ethyl]-4-+ ++piperidinmethanol) caused a complete inhibition of whole-body as well as head jerking. MDL100.151 had only limited effect on myoclonic jerking when given alone. The inhibitory effects of the 5-HT receptor antagonists on either L-5-HTP- or 5-MeODMT-induced myoclonus were found to be very similar. These data confirm a role for the 5-HT1A and 5-HT1B/1D receptors and suggest a role for 5-HT2A receptors in mediating myoclonus in guinea pigs. Moreover, the study shows that by considering head and whole-body jerking as two pharmacologically distinct behavioural responses, subtype specific 5-HT1A, 5-HT1B/1D and 5-HT2A receptor antagonists can be distinguished.
 ...
PMID:Head and whole-body jerking in guinea pigs are differentially modulated by 5-HT1A, 5-HT1B/1D and 5-HT2A receptor antagonists. 986 7

We report a case of autosomal dominantly inherited dystonia and panic attacks to discuss successful treatment of a common serotonergic pathology with medication. The objective analysis of the movement disorder was done by Optotrak. First we demonstrate a reduction of the myoclonus by L-5-hydroxytryptophan, which inhibits after 11 months. After changing the medication to Nefadozone, the myoclonus and the frequency of panic attacks were reduced.
 ...
PMID:[Familial myoclonus-dystonia syndrome associated with panic attacks]. 1108 16

The treatment of progressive myoclonus epilepsy (PME) remains a major therapeutic challenge in neurology. Generalized convulsive seizures are often well controlled through classic antiepileptic drugs (AEDs) like valproate and clonazepam, whereas myoclonus, the main symptom that is affecting patients most in their daily life, is usually refractory to standard AEDs. Alternative therapy concepts have been and still are investigated. Among the new drugs, zonisamide and piracetam have shown the most promising results as add-on treatments. Other therapeutic approaches, like the use of antioxidants, 5-hydroxytryptophan (5-HTP), and baclofen should also be taken into consideration for the treatment of intractable cases of PME. Nonpharmacologic treatment options such as diet and physical therapy should always be considered, because they may save costs and side effects. In some instances, the occasional use of alcohol has shown beneficial effects.
 ...
PMID:Progressive Myoclonic Epilepsies. 1173

Aromatic L-amino acid decarboxylase (AADC) is a vitamin B 6 requiring enzyme involved in the biosynthesis of the neurotransmitters dopamine (DA) and serotonin. Lack of AADC leads to a combined deficiency of the catecholamines DA, norepinephrine (NE), epinephrine (E) as well as of serotonin. Here we describe premature twins who presented with severe seizures, myoclonus, rotatory eye movements and sudden clonic contractions. The patients showed an improvement of the clonic contractions under vitamin B 6 supplementation but died in the third week of life. In CSF and urine a biochemical pattern indicative of AADC deficiency was revealed. Concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were decreased, in association with increased concentrations of 3-ortho-methyldopa (3-OMD) in CSF and significantly increased vanillactic acid in urine. The AADC enzyme substrates L-dopa and 5-hydroxytryptophan (5-HTP) were elevated in CSF. Elevated concentrations of threonine as well as of an unidentified compound in CSF rounded off the biochemical pattern. AADC activity was found to be increased in plasma and deficient in the liver. Molecular studies effectively ruled out a genetic defect in the AADC gene. The basis for the epileptic encephalopathy in the twins may be located in the metabolism of vitamin B 6 and remains to be defined.
 ...
PMID:Clinical and laboratory findings in twins with neonatal epileptic encephalopathy mimicking aromatic L-amino acid decarboxylase deficiency. 1220 Jul 39

Determining the precise cause of gait dysfunction in adults is often difficult because of the multifactorial nature of the disorder. Additionally, elderly patients have other comorbidities that further complicate their diagnosis. A proper history and physical examination, however, often allow the clinician to arrive at the correct diagnosis. Once a diagnosis is reached, appropriate therapeutic decisions can be made. Patients presenting with Parkinsonism need a thorough evaluation to rule out potentially reversible conditions, such as normal pressure hydrocephalus. Patients with idiopathic Parkinson's disease usually develop gait difficulty and freezing episodes late in the course of the illness. Another important cause of gait disturbance in adults is the cerebellar ataxias. Among the sporadic forms, gluten sensitivity is an important consideration. Identification of this entity is important, because the disease process can be halted with a gluten-free diet. Another group is the paraneoplastic ataxias, which can often be diagnosed in the proper clinical setting. Most of the adult-onset hereditary ataxias are autosomal dominant conditions. Except for the episodic ataxias, treatment of these conditions has been disappointing. Mixed results have been obtained with the use of amantadine, buspirone, and 5-hydroxytryptophan. Physical therapy plays an important role in the gait rehabilitation of these patients. Over the past several years, researchers have developed a greater understanding of motor control and how it relates to freezing. Clinicians can now train patients to use external cues to overcome their motor blocks. Another important advance has been the development of subthalamic nucleus deep brain stimulation in the treatment of patients with troublesome peak dose dyskinesia and other motor fluctuations. Subthalamic nucleus deep brain stimulation should be considered when best medical treatment fails. Cortical myoclonus can be treated with levetiracetam, which has US Food and Drug Administration approval as an antiepileptic agent. It has been quite effective in the treatment of myoclonus and should be considered when other medications fail.
 ...
PMID:Gait and Balance Dysfunction in Adults. 1262 66


<< Previous 1 2 3 4 5 6 7 8 9