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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotoxin-induced lesions of 5-HT neurons produce supersensitivity of 5-HT1 receptors without affecting 5-HT2 receptor binding in the brain. This model was used in the present work to analyze the role of 5-HT receptor subtypes in the mechanism controlling the excitatory and inhibitory behavioral responses to the pharmacological stimulation of 5-HT systems. Dorsalis raphe (DR) lesions were made by stereotaxic injection of kainic acid. At day 30 after injection DR-and control rats displayed similar baseline behavior in hole board tests. Three days later DR-and control rats received an ip injection of fluoxetine (5 or 10 mg/kg) 30 min before injecting ip 5-HTP(15 or 30 mg/kg). Immediately before and after each ip injection the excitatory response (myoclonic syndrome) was evaluated. DR-and control-group showed similar scores of myoclonus in response to fluoxetine-5-HTP. The inhibitory response was investigated in hole board trials performed 30 min after the second ip injection. The DR lesion potentiated the behavioral depressive effect of fluoxetine-5-HTP. In agreement with data in the literature the DR lesion caused 74.9% loss of forebrain 5-HT and 75% increases of 3H-5HT binding in cortex membranes. Most components of the excitatory response, which remained unchanged in the DR-lesioned rats, might be related to 5-HT2 receptors. The increased inhibitory response to 5-HT stimulation in DR-lesioned rats would be due to the supersensitivity of 5-HT1 receptors.
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PMID:Excitatory and inhibitory behavioral responses to the pharmacological stimulation of serotonergic function in dorsalis raphe lesioned rats. 326 46

The central effects of carboxyethyl-gamma-aminobutyric acid (CEGABA) have been studied both in rabbits and in the guinea pig myoclonus model. This drug caused EEG synchronization and behavioural sedation both after intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in a dose-dependent manner, in rabbits. CEGABA showed a protective action against myoclonus induced by means of L-5-HTP in young guinea pigs. These data substantiate the hypothesis that CEGABA is a drug active on the central nervous system and probably exerts its action by strengthening cortical inhibition and/or directly acting on lower brainstem.
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PMID:Experimental study on central effects of carboxyethyl-gamma-aminobutyric acid (CEGABA). 326 35

This chapter concerns palatal myoclonus. Indeed Spencer's vivid nystagmus is now abandoned in favor of the less ambiguous myoclonus. The clinical data are reviewed: its appearance, rhythmic frequency, delay with respect to the causal lesion, resistance to most external influences, and possible associations. The most frequent lesion associated with this clinical phenomenon is a special type of degeneration with hypertrophy of the olivary nucleus of the medulla oblongata, on the side opposite the myoclonus when it is unilateral. This degeneration is usually secondary to a primary lesion, located either in the ipsilateral (to the hypertrophied olive) central tegmentum tract or in the contralateral dentate nucleus, through a specific dentatoolivary pathway. The probable existence of this pathway is confirmed by the demonstration of a topographic relationship between dentate nucleus and contralateral inferior olive and by its delineation in the vicinity of the red nucleus where the superior cerebellar peduncle crosses the central tegmental tract. The mechanisms of these lesions and their ensuing symptoms are discussed. It is suggested that there is a transsynaptic degeneration probably disclosing an archaic phenomenon. Few drugs influence this steady abnormal movement: 5-HTP and carbamazepine recently have been credited with some success.
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PMID:Palatal myoclonus. 348 55

Myoclonus could not be induced in rats with either L-5-HTP alone or hypoxia. Following amine depletion or destruction of the serotonin neurons with 5,7-DHT, myoclonus appeared as part of a complex serotonergic behavioral syndrome induced by serotonin agonists. On the other hand, in the guinea pig, L-5-HTP induces a pure myoclonic syndrome in a dose-dependent fashion. Myoclonus also was induced by injection of serotonin into the dorsal pons of the guinea pig. This is additional evidence confirming the importance of the brainstem structures in the L-5-HTP guinea pig model of myoclonus. Deoxyglucose (DG) autoradiography in guinea pigs following systemic L-5-HTP administration demonstrated increased glucose metabolism within thalamic and third nerve nuclei, with decreased metabolism in the cortex, and the molecular layer of the hippocampus. Since serotonin is an inhibitory transmitter, we hypothesize that the decreases observed in cortex may be the result of direct serotonergic inhibition, whereas the increases observed in the thalamus probably represent indirect effects via polysynaptic pathways.
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PMID:Serotonin models of myoclonus in the guinea pig and rat. 348 58

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

Eegraphic, behavioural, autonomic changes were studied in rabbits, after intravenous (i.v.) administration of L-5-hydroxytryptophan (L-5-HTP) and intracerebroventricular (i.c.v.) administration of ketanserin. The cerebral electrical activity on cortex and Cornu Ammonis dorsale (CAd) was evaluated by means of quantitative EEG analysis. The two drugs induced specific changes in all the parameters examined. L-5-HTP caused stereotyped movements typical of the serotoninergic syndrome and EEG "arousal" pattern. Ketanserin did not induce any behavioural change; quantitative EEG analysis showed an increase in those parameters typical of "slow sleep" pattern. The changes caused in guinea pigs by pretreatment with ketanserin, in the experimental model of myoclonus induced by L-5-HTP, were investigated. In the present study the possible mechanisms of action which subtend these results are discussed.
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PMID:Neuropharmacological profile of ketanserin. 349 32

Administration of p,p'-DDT to rats produced myoclonus, but unlike previous studies in mice, this was not decreased by administration of clonazepam. Precursors of 5-hydroxytryptamine (5-HT) (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists, quipazine and Org 6582 did not. Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT. Drugs altering the function of dopamine and noradrenaline (apomorphine, clonidine or phenoxybenzamine) also had no effect on this myoclonus. Administration of monoamine oxidase inhibitors (MAOIs; pargyline, nialamide and tranylcypromine) markedly attenuated the myoclonus, an effect that could not be attributed to an action on any one monoamine system. No observable changes in cerebral biochemical parameters of 5-HT occurred at the onset of myoclonus, although tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in brain were increased following periods of prolonged myoclonus. Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem. Although this was similar to electrophysiological findings in some human patients with post-anoxic action myoclonus, the pharmacological studies suggest that the myoclonus induced by p,p'-DDT in the rat is not a suitable model for screening potential drugs to be used in the treatment of this disorder.
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PMID:Myoclonus in the rat induced by p,p'-DDT and the role of altered monoamine function. 402 63

In male Swiss mice, muscimol produced myoclonic jerks. A 3 mg/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain serotonin levels by the administration of 5-hydroxytryptophan (80-160 mg/kg) in combination with a peripheral decarboxylase inhibitor resulted in an inhibition of the muscimol effect. However, in a similar experiment l-dopa (80-160 mg/kg) was without effect. In doses of 3-10 mg/kg, the serotonin receptor agonist MK-212 caused a dose-dependent blockade of the response of muscimol. Of the benzodiazepines, clonazepam (0.1-0.3 mg/kg) was found to be several fold more potent than diazepam (0.3-3 mg/kg) in blocking the myoclonic jerks. While (-)-baclofen (1-3 mg/kg) proved to be an effective antagonist of muscimol, its (+)-isomer (5-20 mg/kg) lacked this property. Considering the fact that 5-HTP and the benzodiazepines have been found to be beneficial in the management of clinical myoclonus, the muscimol-induced myoclonus seems to be a satisfactory animal model that may prove useful for the development of new drug treatments for this condition. Our present study indicated the possible value of MK-212 and (-)-baclofen in the management of clinical myoclonus.
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PMID:Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice. 611 80

L-5-Hydroxytryptophan (5HTP) (with or without carbidopa pretreatment), L-tryptophan (plus pargyline pretreatment), or tryptamine (plus pargyline pretreatment) all induced dose-dependent myoclonus in guinea pigs. At the time of maximal behavioural response animals were killed for determination of brain indoleamine content. Administration of 5HTP (50-200 mg/kg) to naive guinea pigs, or of 5HTP (20-80 mg/kg) to carbidopa- (25 mg/kg 1 hr previously) pretreated animals, markedly elevated brain 5-hydroxytryptamine (5HT) concentrations but depressed whole brain tryptamine content. L-Tryptophan (50-200 mg/kg) administration to pargyline- (75 mg/kg 30 min previously) pretreated animals also increased cerebral 5HT levels. L-Tryptophan (200 mg/kg plus pargyline), elevated whole brain tryptamine content. Administration of tryptamine (40 mg/kg) to pargyline-pretreated guinea pigs caused a small increase in brain 5HT levels, but markedly elevated cerebral tryptamine content. 5HT appears to be the indoleamine mainly responsible for 5HTP-induced myoclonus but tryptamine predominates in tryptamine-induced myoclonus. Both 5HT and tryptamine may contribute to myoclonus induced by L-tryptophan.
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PMID:Alterations in brain 5HT and tryptamine content during indoleamine-induced myoclonus in guinea pigs. 619 24

Six patients with myoclonus were given 0.1-0.15 mg lisuride i.v. All patients had stimulus-sensitive myoclonus and an increased size of somatosensory evoked potentials, and in three there was electrophysiological evidence of a cortical event time-locked to the jerks. All subjects showed a considerable diminution of spontaneous, action- and stimulus-evoked jerking. Lisuride has potent central dopaminergic and serotonergic actions. Administration of the dopamine agonists levodopa or apomorphine had no effect on myoclonic jerking in any of the six patients. Detailed pharmacological analysis of the myoclonus in one patient showed that levodopa, apomorphine, and haloperidol had no effect, and that haloperidol did not prevent the therapeutic action of lisuride. 5-Hydroxytryptophan abolished the myoclonus, and methysergide prevented the beneficial effect of lisuride, although it did not alter spontaneous myoclonus. These observations suggest that lisuride improves some types of reflex, stimulus-sensitive cortical myoclonus by a serotonin agonist action.
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PMID:Cortical reflex myoclonus responds to intravenous lisuride. 641 86


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