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

Lines of mice selectively-bred for High and Low-Activity in an open-field maze were tested for seizure susceptibility to three analeptics: flurothyl, pentylenetetrazol and bicuculline. The major finding was that two replicate High-Activity lines were more susceptible to myoclonic convulsions but less susceptible to clonic convulsions than their respective replicate Low-Activity lines. The major exception to this finding was that the High and Low-Activity lines did not differ for bicuculline-induced clonus although females tended to conform to the general pattern. These results are interesting because they demonstrate that diametrically opposite susceptibility to myoclonus and clonus is not an isolated phenomenon. Similar seizure susceptibility patterns and activity differences have also been reported for the Long-Sleep and Short-Sleep selectively-bred mouse lines. Further, since the progenitor population of the High-Activity and Low-Activity lines were developed from strains that were also part of the progenitor population of the Long-Sleep and Short-Sleep lines, it is hypothesized that some of the same alleles underwent selection in both selective-breeding programs.
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PMID:Differential convulsive susceptibility of high-activity and low-activity selected mice in response to GABA antagonists. 356 1

Dementias which are either reversible or avoidable are discussed in the light of the literature. The frequency is between 6 and 32%. The most important etiological groups are immunological vasculopathies, hyperlipidemia, some types of encephalitis and, mainly, progressive dementia of the insane, benign tumors and in particular meningioma, low pressure hydrocephalus, intoxications due to drugs, industrial products and alcohol, metabolic disturbances, encephalopathy in dialysed patients, ileo-jejunal-bypass encephalopathy and encephalopathy due to neoplasms. Dementias are also seen in endocrinological disturbances and particularly in hypothyroidism. Vitamin B12 and folate deficiency, as well as epilepsy, may be causes of dementia. Depression may mimic a state of dementia. Some features of reversible dementias are listed, including in particular the somewhat more rapid onset, the younger age of patients, and accompanying neurological symptoms such as headache, gait disturbances, ataxia, polyneuropathy, myoclonus or epileptic fits.
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PMID:[Reversible and preventable dementias]. 361 87

The behavioral and electrographic effects of chronic (7 days), localized infusion of GABA (100 micrograms/microliter) into the somatomotor cortex of fully amygdala-kindled rats is reported. The animals were stimulated once daily until a stage 5 (generalized clonic seizure) was obtained for five consecutive days. After determination of a stable seizure triggering threshold, the rats were implanted with osmotic minipumps (1 microliter/h for 7 days) connected to previously implanted bilateral cannulae. Amygdala stimulation was continued for 14 successive days. GABA infusion reduced the motor seizure without significantly modifying the limbic afterdischarge. This effect lasted until termination of drug application, with recovery of stage 5 convulsions on the following 3 to 5 days. No effects were observed in saline-infused animals or in rats with unilateral GABA treatment. Upon cessation of GABA treatment (removal of the osmotic devices by day 7 postimplantation), spontaneous epileptic discharges localized to the infusion sites appeared. In some animals, the abnormal activity was accompanied by behavioral signs of myoclonus. This cortical hyperexcitability lasted 2 to 24 h, with complete recovery afterward. These data indicate that two types of focal epilepsy may coexist independently in the same animal and provide confirmation of previous observations in the monkey on the existence of a "GABA-withdrawal syndrome" after chronic, focal infusion of the amino acid.
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PMID:Anticonvulsant effect of intracortical, chronic infusion of GABA in kindled rats: focal seizures upon withdrawal. 365 26

Photosensitivity was acquired as a result of kindling in the lateral geniculate body (GL), and the GL-kindled cat pretreated with DL-allylglycine showed a stable level of photosensitivity. To test the usefulness as a model for the evaluation of anticonvulsant drugs, the effects of phenobarbital (PB) and phenytoin (PHT) on photosensitivity were studied in the GL-kindled cat under DL-allylglycine. PB (5 and 10 mg/kg intravenously, i.v.) completely suppressed photically induced seizures in most subjects at plasma concentrations of 7-16 micrograms/ml, and this anticonvulsant action persisted for at least 4 h after the injection. PHT (15 mg/kg, i.v.) at plasma concentrations of 9-15 micrograms/ml produced toxic signs, e.g., pupil dilatation, hypersalivation, and tachypnea. At this dose, PHT was inactive against photically induced myoclonus but prevented the elicitation of a generalized tonic-clonic convulsion. From these results showing that the effects of anticonvulsant drugs on photically induced seizures can be assessed in relation to plasma concentration and acute neurologic toxicity, we suggest that the GL-kindled cat is a potentially useful animal model of epilepsy for testing the efficacy of anticonvulsant drugs.
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PMID:A new experimental model for drug studies: effects of phenobarbital and phenytoin on photosensitivity in the lateral geniculate-kindled cat. 369 16

The effects of DL-allylglycine, an inhibitor of GABA synthesis, on the responses to photic stimulation were studied in the cat kindled in the lateral geniculate body (GL). For 3 to 8 h after the injection of DL-allylglycine at a subconvulsant dose (30 or 40 mg/kg, i.v.), the kindled cat showed a stable level of photosensitivity without any toxic effects and responded with various degrees of myoclonus or a generalized tonic-clonic convulsion when photic stimulation was repeated at hourly intervals. The incidence of photically induced myoclonus reached its plateau during this period. Our results suggest that photosensitivity of the lateral geniculate-kindled cat is related to the modification of GABAergic mechanisms, and that when the GL-kindled cat is pretreated with DL-allylglycine it is a reliable model of photosensitive epilepsy.
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PMID:Effects of allylglycine on photosensitivity in the lateral geniculate-kindled cat. 375 82

Irrespective of the etiology, a water and electrolyte imbalance provoking a hypo- or hyperosmolar state causes metabolic encephalopathy, as may occur with any metabolic disturbance. The pathophysiology of metabolic encephalopathy relies on a diffuse neuronal dysfunction which occasionally shows a focal maximum. To the clinician it presents in the form of nonspecific symptoms or signs, such as altered level of alertness or awareness of the environment, or impaired attention, cognition or orientation. When the onset of hypo- or hyperosmolality is rapid, delirium may develop or the level of consciousness can decrease to the point of coma. Myoclonic jerks, gait disturbance and focal or generalized fits are additional nonspecific signs. When the water and electrolyte imbalance coincides with or is caused by brain disease, the signs of the two conditions are added. On the other hand, complicating hemorrhages, sinus thrombosis, or brainstem herniation or compression may be taken for a primary structural brain lesion, and the water and electrolyte imbalance may easily be overlooked. Pathophysiology, symptoms and signs, and therapy of hypo- and hyperosmolar states are discussed. Central pontine myelinolysis is considered separately.
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PMID:[Neurologic manifestations of osmolality disorders]. 389 13

There were marked strain differences in the duration of the protective effects of diazepam against the convulsant actions of penylenetetrazole and picrotoxin in mice. In no case was significant protection found at 12 h or longer, regardless of whether the incidence of or the latencies to myoclonus or tonic-clonic convulsions were considered. These behavioural differences could not be explained simply in terms of strain differences in benzodiazepine metabolism or in percent of receptor occupancy, as determined by the fractional displacement of 3H-flunitrazepam binding in vivo. It is suggested that there might be strain differences in the percent of receptor occupancy needed in order to produce an anticonvulsant effect.
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PMID:Long-lasting anticonvulsant effects of diazepam in different mouse strains: correlations with brain concentrations and receptor occupancy. 392 50


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