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)

We used saturation radioligand binding to measure nine types of serotonin receptors in 13 neuroblastomas from children. 5-HT1E and 5-HT3 sites were found in neuroblastomas with receptor density and affinity similar to human or rat brain. No 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, or 5-HT uptake sites were found in any of the tumors, although all were detected in human or rat brain. These data demonstrate that human neuroblastomas possess 5-HT receptors found in human brain and relevant to human myoclonus. We speculate that 5-HT receptors in human neural crest-derived tumors may have clinical and neurobiological significance.
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PMID:Serotonin receptors in human neuroblastoma: a possible biologic tumor marker. 153 97

The brainstem is the locus of serotonin (5-HT)-mediated myoclonus in the guinea pig, which is induced by 5-hydroxy-L-tryptophan (L-5-HTP) and indole but not piperazine 5-HT receptor agonists. As an initial step in testing the hypothesis that one 5-HT receptor subtype mediates this effect, we measured seven 5-HT receptor binding sites and the 5-HT uptake site in guinea pig brainstem and compared them to the rat. In guinea pig brainstem, the rank order of binding site density was: 5-HT transporter site >> 5-HT1D > antagonist-labeled 5-HT2 > 5-HT1A, 5-HT1C > 5-HT1E > agonist-labeled 5-HT2 binding site. There were fewer 5-HT1A and 5-HT1C binding sites and 5-HT uptake sites in guinea pig than rat brainstem, more 5-HT1D and antagonist-labeled 5-HT2 sites, but the differences were 2-fold or less. The major species difference was that 5-HT1B sites were virtually undetectable in guinea pig brainstem. Limited competition experiments with related 5-HT receptor subtype-selective agonists and antagonists suggested that the sites in guinea pig brainstem conformed to those described in the rat. 5-HT agonist and antagonist dose-threshold and dose maximum-effect data from guinea pig myoclonus in vivo were compared with receptor affinities at each receptor site in vitro from the literature. No convincing correlation between myoclonus and one particular 5-HT site was found. These data indicate the presence of a full complement of 5-HT receptor binding site subtypes in guinea pig brainstem with some species differences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brainstem serotonin receptors in the guinea pig: implications for myoclonus. 847 16

The immediate serotonin (5-HT) precursor, 5-hydroxy-L-tryptophan (L-5-HTP), is an investigational treatment for myoclonic disorders. Its mechanism of action in humans is incompletely understood. We measured the density of subtypes of 5-HT1 and 5-HT2 receptors and the affinity of 5-HT and L-5-HTP in vitro in the human brainstem and cortex, regions associated with subcortical and cortical myoclonus, respectively. In the cortex, the rank order of 5-HT receptor subtype Bmax was 5-HT2A (low-affinity), 5-HT1A, 5-HT uptake sites, 5-HT1D, 5-HT2C, 5-HT1E/F, and 5-HT2A (high-affinity) sites. In the brainstem, the rank order was 5-HT uptake sites, 5-HT1D, 5-HT2C, 5-HT1A, and 5-HT2A(L) sites. Specific binding at 5-HT1E/F and high-affinity 5-HT2A sites was too low for characterization. In competition studies, 5-HT had high affinity for 5-HT1A and 5-HT2C sites in the brainstem and cortex, but L-5-HTP was > 1,000-fold less active. These data support the hypothesis that in humans L-5-HTP stimulates 5-HT receptors in the CNS only after conversion to 5-HT. They also indicate in the human brainstem a prominence of 5-HT1A sites and paucity of 5-HT1D, 5-HT1E/F, and 5-HT2A sites, which has implications for brainstem-mediated myoclonus and response to serotonergic drugs.
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PMID:Human brainstem serotonin receptors: characterization and implications for subcortical myoclonus. 893 89

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.
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PMID:5-Hydroxytryptophan-induced myoclonus in guinea pigs: mediation through 5-HT1/2 receptor subtypes. 965 Aug 47