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)

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

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.
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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

d-Fenfluramine is a potent serotonin (5-HT) reuptake inhibitor/releaser and, until its recent recall, was prescribed as an anoretic agent. This study demonstrates that 10 mg/kg d-fenfluramine i.p., when administered to rats in a warm (27 degrees C) environment, produces neuronal degeneration within select brain regions. Degeneration was detected and localized using a recently developed fluorescent marker of neuronal degeneration, Fluoro-Jade. The most extensive cortical damage was in the anterior cingulate region. In the medial thalamus, degeneration was frequently seen within the intralaminar nuclei, and somewhat less frequently observed within the paraventricular nucleus, the mediodorsal nucleus, and the gelatinosis nucleus. Cerebellar damage occurred primarily in medial Purkinje cells and occasionally in granule cells or basket cells. Degeneration was not observed in either saline-injected control animals or in rats given even higher doses of 25 mg/kg d-fenfluramine but kept in a cooler environment (23 degrees C). The degeneration was clearly most prominent in animals with body temperatures of 41 degrees to 42 degrees C, but this degeneration was not seen in animals given saline that became extremely hyperthermic in a 37 degrees C environment. Behavioral signs such as tremors, myoclonus, rigidity, and splayed legs were seen in all animals with extensive neurodegeneration. The areas damaged by d-fenfluramine, when hyperthermia occurs, could play a role in the expression of the serotonin syndrome. Elevated extracellular 5-HT levels alone are probably not sufficient for neurotoxicity, and additional factors such as hyperthermia, regional specificity of 5-HT receptor subtypes, blood flow, and/or neuronal networks may be involved.
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PMID:d-Fenfluramine produces neuronal degeneration in localized regions of the cortex, thalamus, and cerebellum of the rat. 1033 Jun 89


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