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)

This study evaluated the behavioral elements of three 5-HT-related syndromes (intraperitoneal 5-hydroxytryptophan after intracisternal 5,7-dihydroxytryptamine (DHT), p-chloroamphetamine (PCA), fenfluramine (FF), or combinations of drugs) scored from video-tapes and their relationship to locomotor activity (LMA) photocell recording, regional monoamine concentration and S-1 receptor binding. Rearing was eliminated by drugs which produce the myoclonic syndrome and was the single best indicator of control treatments (saline or 5-HTP in unlesioned rats and saline in DHT-lesioned rats). Global 'abnormality', hunching (rigid arching of back), hindlimb abduction, forepaw myoclonus, stereotyped lateral head movements, backing, and immobility occurred significantly only in drug-treated rats. Multiple forms of myoclonus (appendicular and truncal) and convulsions were dose-dependent drug effects. Both 5-HTP (after DHT) and PCA increased LMA significantly, but hyperactivity induced by PCA could be blocked by giving 5-HTP concomitantly. Substantial 5-HT presynaptic destruction by DHT prevented backing but not other behavioral or locomotor effects of FF and PCA. Drug combinations did not produce additive behavioral effects. Backing, immobility, and locomotor activity best differentiated between drug treatments, and could be used to correctly allocate animals to drug groups. Drug treatments also could be differentiated by reducing the number of behavioral variables into summary variables (principal components) and by discriminant analysis. Only forepaw myoclonus and total behavioral score were correlated with 5-HT concentrations (brainstem), indicating behavioral heterogeneity. Our study suggests that there is a common core 'myoclonic-serotonergic' syndrome (forepaw myoclonus, head weaving, hindlimb abduction, hunching) of stimulation of 5-HT receptors plus additional drug-specific elements (backing, LMA). Although brainstem receptors appear to be an important locus for some of these behaviors, S-1 receptors do not explain the behavioral supersensitivity to 5-HTP in our DHT-lesioned rats.
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PMID:Serotonin-lesion myoclonic syndromes. II. Analysis of individual syndrome elements, locomotor activity and behavioral correlations. 348 93

The neuropharmacologic profile of intraperitoneally injected harmala alkaloids and related beta-carbolines was evaluated in the rat. All drugs induced central effects (convulsions, catalepsy, or altered startle), but only harmaline and harmine were tremorogenic at low doses. Methoxylation of the carboline 7 position was requisite for this effect. Coadministration of harmaline (but not harmine) and 5-hydroxytryptophan (tryptamine or m-chlorophenyl-piperazine) induced a lethal convulsive myoclonic syndrome which could not be evoked by either drug separately. Compared with the myoclonic-serotonergic syndrome evoked by 5-hydroxytryptophan in rats with 5.7-dihydroxytryptamine lesions, harmaline+5-hydroxytryptophan-treated rats displayed more continuous and greater axial myoclonic jerks and some postural differences. Clorgyline or tranylcypromine but not pargyline could be substituted for harmaline. The harmaline syndrome was blocked by the benzodiazepine agonists, physostigmine and verapamil. The harmaline+5-hydroxytryptophan syndrome was blocked by drugs acting at benzodiazepine receptors (CL 218,872 greater than ethyl-beta-carboline-3-carboxylate, clonazepam, diazepam, Ro 15-1788, pentobarbital), and baclofen. Naloxone, benztropine, quipazine, and apomorphine had partial effects, and calcium channel blockers prevented death but did not prevent convulsions. 5-Hydroxytryptamine antagonists were poor blockers, although cyproheptadine and ketanserin significantly reduced mortality. Phenobarbital was more effective than other anticonvulsants. Lesion studies suggested a role for monoaminergic neurons and the inferior olive in the expression of the harmaline+5-hydroxytryptophan syndrome. These data describe a complex convulsive myoclonic syndrome that is behaviorally related to but pharmacologically distinct from the serotonin syndrome, which may be useful in studying serotonergic-benzodiazepine interactions in the pathophysiology of myoclonus.
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PMID:Harmala alkaloids and related beta-carbolines: a myoclonic model and antimyoclonic drugs. 349 51

To study the species difference of guinea pigs and rats in response to 5-hydroxytryptophan (5-HTP), we injected both animals intracisternally with 5,7-dihydroxytryptamine. In rats with 5,7-dihydroxytryptamine lesions, 5-HTP evoked the well described myoclonic-serotonergic syndrome. In the guinea pig, 5,7-dihydroxytryptamine lesions significantly increased the severity of myoclonic response to 5-HTP (150 mg/kg) compared to vehicle controls, resulting in lethal convulsions. Guinea pigs treated with 5,7-dihydroxytryptamine did not develop spontaneous myoclonus, or when treated with 5-HTP, other 'serotonergic behaviors' such as lateral head weaving, hindlimb abduction, and forepaw tapping. Guinea pigs tolerated intracisternal 5,7-dihydroxytryptamine less well than rats, with a higher mortality, although immediate post-injection convulsions were less severe and did not require phenobarbital prophylaxis. Staged lower doses of 5,7-dihydroxytryptamine (100-200 micrograms) were better tolerated than a single high dose of neurotoxin (400 micrograms). The regional profile of 5,7-dihydroxytryptamine lesions in the guinea pig resembled that of the rat, with maximal depletion of 5-HT in spinal cord and selected forebrain structures, and little effect in diencephalon and midbrain. Depletions in the guinea pig were less selective for 5-HT using desipramine pretreatment than in the rat. In naive guinea pigs and rats, regional content of 5-HT was similar. These data suggest that the functional integrity of serotonergic neurons is not requisite for the expression of myoclonus induced by 5-HTP in the guinea pig. 5,7-Dihydroxytryptamine lesions in the guinea pig resulted in behavioral and neurochemical similarities and differences in comparison with the rat.
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PMID:The guinea pig myoclonic model: behavioral supersensitivity to 5-hydroxytryptophan induced by intracisternal 5,7-dihydroxytryptamine. 350 Aug 66

We studied the effect of 3-acetylpyridine (3-AP) lesions on the serotonergic-myoclonic syndromes evoked by quipazine (QP), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), fenfluramine (FF), and p-chloroamphetamine (PCA) in the adult rat. Eleven behaviors were scored from videotapes by an observer blind to drug status. In unlesioned rats, drugs could be differentiated by forelimb and axial myoclonus, pivoting and backing. All drugs significantly suppressed rearing. 3-AP produced a lasting action-enhanced body tremor which differed from axial myoclonus in its vertical direction and rhythmicity. 3-AP lesions modified the effect of drugs on several behaviors, increasing axial (QP, FF, PCA) and forelimb (5-MeO-DMT, FF, PCA) myoclonus and decreasing locomotor score. Prior lesions with 5,7-dihydroxytryptamine did not prevent the effect of 3-AP or any behaviors of the serotonin syndrome, but had a slight effect on the magnitude of forelimb myoclonus, head weaving, and hunching induced by some drugs. Neither lesion abolished or reduced myoclonus. These data suggest that intact 5-HT terminals are not requisite for the tremorogenic and cytotoxic effect of 3-AP. To the extent that chemical lesions with 3-AP are selective for the inferior olive (IO), the role of the IO in myoclonus in several 5-HT rodent myoclonic models appears to be regulatory rather than stimulatory.
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PMID:3-Acetylpyridine lesions and four serotonergic behavioral syndromes in the rat. 356 72

Eleven patients with long-standing progressive myoclonus epilepsy, PME, and age- and sex-matched epileptic controls received L-tryptophan (L-Trp) 100 mg/kg body weight combined with carbidopa in addition to their usual anticonvulsant regimen. During six weeks of the trial an improvement in activities of daily living and a decrease of action myoclonus was noted in the PME patients. The frequency of seizures compared with the past year decreased significantly in the PME patients, but not in the epileptic controls. Changes in the EEGs of the PME patients were scant, but a slight decrease was noted in myoclonic spikes. Both plasma Trp and platelet 5-HT increased significantly and at least as much as in epileptic controls. 5-HIAA and HVA concentrations in the CSF of the PME patients increased significantly during the trial. The results support previous findings concerning Trp treatment in PME, and longer trials with Trp + carbidopa could be of value in this disease.
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PMID:L-tryptophan-carbidopa trial in patients with long-standing progressive myoclonus epilepsy. 617 51

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

Locomotor activity and hole-board exploration (frequency and time spent head-dipping) were impaired in male rats by injecting IP the 5-HT agonists, fluoxetine and 5-HTP. This treatment produced also myoclonus and increased the time spent resting during trials. The chronic ingestion of chlorimipramine (CIM) or the injection of the 5-HT receptor blocker, methysergide (15 mg/kg) prevented the action of the 5-HT agonists on locomotion and resting and blocked the appearance of myoclonus. Both CIM and methysergide prevented to a minor degree the fluoxetine-5-HTP-induced decrease of exploration. The chronic ingestion of CIM clearly potentiated the effects of methysergide on hole-board exploration. Results suggest that the chronic treatment with therapeutic doses of CIM reduces the functional activity of some 5-HT systems in the brain of the rat, probably by blockade of post-synaptic 5-HT receptors. This does not preclude, however, that CIM may also alter some NA systems.
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PMID:Effects of the chronic ingestion of therapeutic doses of chlorimipramine on the behavioral action of agonists and antagonists of serotonin in male rats. 660 38

We have previously reported the presence of posthypoxic, audiogenic myoclonus in rats after cardiac arrest and the ability of the 5-HT precursor, 5-HTP, to attenuate these muscle jerks. In addition, we have recently shown that 5-HT2 and 5-HT3 agonists can reduce the severity of myoclonus in these animals, suggesting a deficiency in serotonergic neurotransmission. In the present study, the levels of 5-HTP, 5-HT, and 5-HIAA were measured in seven regions of the brain in myoclonic and normal rats to identify the areas of the brain in which a serotonergic dysfunction resides. Similar to previous studies, we observed pronounced posthypoxic, audiogenic myoclonus 3 and 14 days after resuscitation from cardiac arrest, with a resolution of the abnormal movements by 45 days postarrest. HPLC measurements revealed significant changes in indole levels in the following areas of the brain: cortical 5-HIAA, striatal 5-HT, striatal 5-HIAA, hippocampal 5-HT, mesencephalic 5-HIAA, myelencephalic 5-HT, myelencephalic 5-HIAA, cerebellar 5-HTP, and cerebellar 5-HT. The changes in striatal 5-HT, cortical 5-HIAA, and mesencephalic 5-HIAA appear most relevant to the pathophysiology of posthypoxic myoclonus because regression analyses showed significant correlations between the myoclonus scores of the animals and the levels of these indoles. Based on the observed pattern of results, we postulate a dysfunction in serotonergic lateral (cortical) and far lateral (extrapyramidal) ascending pathways in posthypoxic myoclonus.
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PMID:Association between brain indole levels and severity of posthypoxic myoclonus in rats. 754 90

The serotonin syndrome has increasingly been recognised in patients who have received combined serotonergic drugs. This syndrome is characterised by a constellation of symptoms (confusion, fever, shivering, diaphoresis, ataxia, hyperelflexia, myoclonus or diarrhoea) in the setting of the recent addition of a serotonergic agent. The most common drug combinations causing the serotonin syndrome are monoamine oxidase inhibitors (MAOIs) and serotonin selective reuptake inhibitors (SSRIs), MAOIs and tricyclic antidepressants, MAOIs and tryptophan, and MAOIs and pethidine (meperidine). This syndrome is caused by excess serotonin (5-hydroxytryptamine; 5-HT) availability in the CNS at the 5-HT1A-receptor. There may also be some interaction with dopamine and 5-HT2-receptors. This syndrome probably has a low incidence, even among patients taking these drug combinations, and there is likely to be some other as yet unidentified inciting factor causing some patients to develop a full serotonin syndrome. Because fatalities and severe complications have accompanied the serotonin syndrome, the previously described drug combinations should be used cautiously or not at all. The serotonin syndrome is usually mild and, if managed with drug withdrawal and supportive therapy, generally improves within hours. Patients who develop hyperthermia should be treated aggressively with external cooling and paralysis. Methysergide and cyproheptadine appear to be useful adjuncts in treating the serotonin syndrome.
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PMID:The serotonin syndrome. Implicated drugs, pathophysiology and management. 757 68

An abnormality of serotonergic neurotransmission has been hypothesized in p,p'-DDT intoxication to explain myoclonus and the antimyoclonic properties of 5-hydroxytryptophan (5-HTP). To study the role of serotonin (5-HT) receptors in myoclonus induced by p,p'-DDT in the rat, we performed time-course and dose-response studies of the effects of p,p'-DDT on behavior and regional 5-HT1 and 5-HT2 binding sites. At a time when low dose (80 mg/kg) p,p'-DDT elicited stimulus-sensitive and spontaneous myoclonus, there were no significant changes in Bmax or Kd of 5-HT1A, 5-HT1B, 5-HT1C sites in cortex, striatum, brainstem or spinal cord, agonist- or antagonist-labelled 5-HT2 sites in cortex, or 5-HT uptake sites. High dose p,p'-DDT (1000 but not 500 mg/kg), which also induced convulsions, only slightly increased 5-HT1 (unsubtyped) binding sites in cortex but not in brainstem or spinal cord and had no effect on antagonist-labelled 5-HT2 sites. In naive frontal cortex in vitro, 1 microM p,p'-DDT displaced neither [3H]5-HT or [3H]ketanserin specific binding. Lesions of central indoleamine neurons made with 5,7-dihydroxytryptamine significantly prolonged the latency and attenuated the severity of p,p'-DDT behavioral abnormalities, increasing the dose of p,p'-DDT which induced myoclonus (MD50) or convulsions (CD50) in 50 percent of the rats. This is the first report of 5,7-DHT-induced attenuation in the p,p'-DDT myoclonic model.
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PMID:p,p'-DDT myoclonic/epileptic model: serotonin receptor binding and behavioral studies in the rat. 799 Dec 14


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