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)

Tryptamine (1-320 mg/kg) evoked only slight muscle jerking in naive guinea-pigs but, in animals pretreated with pargyline (75 mg/kg; 1 hr previously), tryptamine induced a dose-dependent (6-160 mg/kg) myoclonus. The myoclonus induced by tryptamine (40 mg/kg) plus pargyline (75 mg/kg) was differentially inhibited by the indoleamine receptor antagonists, methergoline (5 mg/kg) which was more potent than methysergide (10 mg/kg), mianserin (10 mg/kg) which was more potent that cyproheptadine (10 mg/kg) and propranolol (20 mg/kg) which was more potent than cinanserin (10 mg/kg). This rank order of potency differed from that observed for the order of potency of these drugs in inhibiting the myoclonus induced by L-5-hydroxytryptophan (5HTP) plus carbidopa in guinea-pigs (Luscombe, Jenner and Marsden, Neuropharmacology, 1981), perhaps indicating involvement of pharmacologically distinct indoleamine receptors. Manipulation of presynaptic function of 5-hydroxytryptamine (5HT) by tryptophan hydroxylase inhibition with p-chlorophenylalanine to produce depletion of cerebral 5HT, or by an L-tryptophan load to elevate 5HT in brain, suggested that the functional integrity of serotonergic neurones is required for the expression of myoclonus induced by tryptamine plus pargyline. A range of blockers of 5HT re-uptake did not alter the jerking produced by tryptamine (40 mg/kg) in guinea pigs pretreated with pargyline (75 mg/kg; 1 hr previously), or the threshold myoclonus induced by a smaller dose of tryptamine (10 mg/kg; plus pargyline 75 mg/kg). It is suggested that myoclonus induced by tryptamine in guinea pigs pretreated with pargyline involves activation of post-synaptic indoleamine receptors by tryptamine by a mechanism which requires intact presynaptic function of 5HT.
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PMID:Tryptamine-induced myoclonus in guinea-pigs pretreated with a monoamine oxidase inhibitor indicates pre- and post-synaptic actions of tryptamine upon central indoleamine systems. 613 Apr 89

1 The physiological, biochemical and pharmacological features of alpha-chloralose-induced myoclonus in the guinea-pig have been studied. 2 EMG bursts in muscles jerking in chloralose-induced myoclonus are long, and are not time-locked to any cortical event recorded in the EEG, although they are evoked by auditory or peripheral nerve stimuli. 3 The efferent conduction velocity down the spinal cord of the signals generating the EMG bursts is fast but the afferent conduction velocity up the cord for stimulus-evoked jerks is slow, in distinction to the reverse characteristics of the spino-bulbo-spinal relfex arc. 4 alpha-Choralose did not cause any consistent change in 5-hydroxytryptamine (5-HT) or 5-hydroxyindoleacetic acid levels in any brain area, nor did it alter 5-HT turnover as judged by the depletion of 5-HT after p-chlorophenylalanine pretreatment. 5 Pretreatment of animals with drugs that increase brain 5-HT action (L-tryptophan with a monoamine oxidase inhibitor, or 5-hydroxytryptophan), or antagonize the action of 5-HT (cyproheptadine) did not abolish or obviously increase chloralose-induced myoclonus. 6 Chloralose-induced myoclonus is not similar to 5-HT-sensitive reticular reflex myoclonus in man.
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PMID:Observations on chloralose-induced myoclonus in guinea-pigs. 615 35

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

In guinea pig brain stem preparations [3H]5-hydroxytryptamine (5HT) bound specifically to both high and low affinity sites, but specific [3H]spiperone binding was low and could not be consistently detected. This indicates a prevalence of 5HT-1 type receptors in this tissue. High affinity-specific [3H]5HT binding was more potently displaced by indole-containing 5HT agonists than by piperazine-containing 5HT agonists. This agreed with the observation that indole-containing, but not piperazine-containing compounds induced dose-dependent myoclonus in guinea pigs which originates from brain stem. The capacity of indoleamine antagonists to displace [3H]5HT-specific binding from guinea pig brain stem was similar to their reported potency in displacing [3H]5HT from 5HT-1 receptors. The [3H]5HT-labelled binding site in guinea pig brain stem is a 5HT-1 receptor and appears to be responsible for the induction of indoleamine-dependent myoclonus.
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PMID:Correlation of [3H]5-hydroxytryptamine (5HT) binding to brain stem preparations and the production and prevention of myoclonus in guinea pig by 5HT agonists and antagonists. 649 22

Myoclonic jerking in guinea pigs originates from the brainstem. Indole-containing 5-hydroxytryptamine (5-HT) agonists, but not piperazine-containing 5-HT agonists, induced myoclonus in guinea pigs at pharmacologically relevant doses. Guinea pig brainstem preparations possessed specific binding sites for [3H]5-HT but specific [3H]spiperone binding was low and inconsistent. 5-HT-1 receptors appear to predominate in this tissue. High affinity [3H]5-HT binding was potently displaced by indole-containing 5-HT agonists but only weakly displaced by piperazine-containing 5-HT agonists. The [3H]5-HT specific binding site in guinea pig brainstem responsible for the induction of indoleamine-dependent myoclonus has the characteristics of a 5-HT-1 receptor.
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PMID:5-Hydroxytryptamine (5-HT)-dependent myoclonus in guinea pigs is induced through brainstem 5-HT-1 receptors. 672 93

L-5-Hydroxytryptophan (5HTP) induces in guinea pigs a myoclonic jerking which is dependent upon stimulation of brainstem 5-hydroxytryptamine (5HT) receptors. We have investigated the ability of 5HT precursors and a range of synthetic 5HT agonists to produce myoclonus. The 5HT precursors and 5HT agonists containing an indole nucleus induced dose-dependent jerking in guinea pigs. In contrast, 5HT agonists possessing a piperazine moiety induced occasional jerking only at toxic doses, but not a those doses normally associated with 5HT agonist activity. The difference in activity between the indole-containing compounds and piperazine-containing 5HT agonists suggests that myoclonus is due to activation of an indole-selective brainstem 5HT receptor and provides further evidence for multiple cerebral 5HT receptors.
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PMID:Myoclonus in guniea pigs is induced by indole-containing but not piperazine-containing 5HT agonists. 708 78

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

The administration of 2,2',2''-tripyridine produced generalized tremor, myoclonus, and hindlimb abduction, similar to the "5-hydroxytryptamine (5-HT) syndrome," in mice. Pretreatment with mianserin, cyproheptadine, methysergide, or metergoline ameliorated, whereas 5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), or 8-hydroxy-2-[di-n-propylamino]tetraline hydrobromide (8-OH-DPAT) augmented the 2,2',2''-tripyridine-induced tremor. Furthermore, diazepam and flunitrazepam exhibited a dose-dependent protection against 2,2',2''-tripyridine-induced tremor in mice, but pentobarbital only had a slightly protective effect. The inhibitory effects of diazepam and flunitrazepam on the 2,2',2''-tripyridine-induced tremor were potentiated in mice pretreated with p-chlorophenylalanine (PCPA). These observations suggest a serotonin-mediated action of 2,2',2''-tripyridine in its tremor action and that the benzodiazepine agonist attenuation of the 2,2',2''-tripyridine-induced tremor is probably mediated through the GABAergic inhibition of serotonergic neurons.
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PMID:Modification of 2,2',2''-tripyridine-induced tremor in mice by serotonergic agonists and antagonists and benzodiazepines. 793 20

Following 10 min cardiac arrest and resuscitation, male Sprague-Dawley rats developed posthypoxic myoclonus. This phenomenon peaked at 14 days and disappeared by 60 days after cardiac arrest. From previous results, the 5-hydroxytryptamine (5-HT) system was implicated in the pathogenesis of the disease. In the present study, we investigated the involvement of 5-HT1A receptors in posthypoxic myoclonus in rats. Single injections of 5-HT1A agonists, buspirone (5 and 10 mg/kg body wt.) or 8-OH-DPAT (1, 2, and 4 mg/kg), had no effect on either the intensity or time course of the disease. In contrast, multiple injections (twice a day for 7 or more days) of buspirone (10 mg/kg) or 8-OH-DPAT (4 mg/kg) significantly attenuated the myoclonus scores of animals (p < 0.05). The results indicate that chronic stimulation of 5-HT1A receptors in the brain may accelerate endogenous compensatory mechanisms and shorten the time course of the disease.
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PMID:Chronic treatments with 5-HT1A agonists attenuate posthypoxic myoclonus in rats. 854 77

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


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