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)

Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5-HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences.
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PMID:Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5-hydroxytryptophan in the rat. 258 10

There have been few previous studies of the functional significance of 5,7-dihydroxytryptamine (5,7-DHT) lesions made in neonatal rats. To study the role of serotonin (5-HT) in recovery of function, rat pups and adult rats were injected intracisternally with 5,7-DHT or saline and challenged acutely with the 5-HT precursor 5-hydroxytryptophan (5-HTP) 4 weeks later as a test of behavioral supersensitivity. Compared to 5,7-DHT lesions in adults, neonatal lesions induced significantly greater 5-HT depletions in brainstem, but 5-HT depletions in other regions were not significantly different in the two groups. Rats with early 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP, consisting of all the component myoclonic-serotonergic behaviors seen in rats with 5,7-DHT lesions made as adults. However, there was significantly less 5-HTP-evoked head weaving, truncal myoclonus and shaking behavior in rats treated with 5,7-DHT as neonates. Body weight was reduced both in rats with early and late 5,7-DHT lesions, but reduction persisted in rats with early lesions. These data indicate overall similarity with some differences between neurochemical and behavioral effects of early and late 5,7-DHT lesions made by the intracisternal route. They suggest that recovery mechanisms did not occur or failed to reverse the neurochemical or behavioral consequences of early 5,7-DHT lesions.
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PMID:Intracisternal 5,7-dihydroxytryptamine lesions in neonatal and adult rats: comparison of response to 5-hydroxytryptophan. 278 68

The effects of some biologically active metabolites of tryptophan on the high pressure neurological syndrome (HPNS) were studied. Kynurenic acid, quinolinic acid, 5-hydroxytryptophan, kynurenine and 3-hydroxyanthranilic acid, at doses within the physiological range, were administered exogenously to rats prior to exposure to increased pressure and any effects on the tremor, myoclonus and convulsion end points of the high pressure neurological syndrome were observed. Quinolinic acid (25 and 50 mg/kg) and kynurenine (50 mg/kg) reduced the onset pressure for tremor, but not myoclonus or convulsions. Kynurenic acid (100 mg/kg) increased tremor onset pressure; 5-hydroxytryptophan (20 mg/kg) slightly increased onset pressure for tremor but decreased that for myoclonus. 3-Hydroxyanthranilic acid (20 mg/kg) had no significant effect on any of the motor signs of the syndrome. These data provide further support for the idea that the motor events seen in the high pressure neurological syndrome are not produced by a single mechanism. Differences between the responses to related metabolites suggest that the precise balance between compounds such as kynurenic acid and quinolinic acid may be important in the appearance of the high pressure neurological syndrome.
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PMID:The effects of kynurenic acid, quinolinic acid and other metabolites of tryptophan on the development of the high pressure neurological syndrome in the rat. 292 79

Although relatively few drugs that specifically influence serotonin neurons have been used in humans, a wide variety of drugs has been used to modify serotonergic function in experimental animals. Several classes of agents increase serotonergic function. These include serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) and monoamine oxidase inhibitors, which elevate serotonin stores; uptake inhibitors and releasers, which increase the concentration of serotonin in the synaptic cleft; and direct serotonin agonists, which mimic the action of serotonin on synaptic receptors. In addition, several kinds of drugs decrease serotonergic function, including serotonin depletors and agents that destroy serotonin neurons, as well as direct serotonin-receptor antagonists. The array of drugs now available improves the opportunities for clarifying the physiological roles of serotonin and gives promise of several therapeutic applications, including treatment of myoclonus.
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PMID:Biochemical pharmacology of the serotonin system. 293 68

The capacity of the putative S2 serotonin receptor antagonists, pirenperone, pipamperone, ketanserin and cinanserin, to block the myoclonic syndrome produced by 30 mg/kg of L-5-hydroxytryptophan (5-HTP) [after lesioning 5-hydroxytryptamine (serotonin, 5-HT)-containing neurons with 5,7-dihydroxytryptamine (DHT)] or 15 mg/kg of fenfluramine (FF) or p-chloroamphetamine (PCA) was tested in adult male Sprague-Dawley rats. S2 antagonists inhibited limb (arrhythmic and asynchronous) and axial (truncal) myoclonus in a dose-dependent manner in the rank order of potency: pirenperone greater than pipamperone greater than ketanserin = cinanserin. Abnormal movements (myoclonus, lateral head weaving) of the myoclonic syndromes were better antagonized than postural abnormalities (hindlimb abduction, hunching of back). Centrally acting drugs, selective for S2 receptors (pirenperone, pipamperone), exhibited greater antimyoclonic properties than the non-selective 5-HT antagonist methysergide, which was as effective as ketanserin and cinanserin. Significant non-specific reduction in myoclonus without the improvement of other behavioral responses followed treatment with sedative/neuroleptic drugs, such as haloperidol (but not the non-neuroleptic dopamine antagonist sulpiride), clonazepam and diazepam. The anticonvulsants valproic acid (100 and 300 mg/kg), adrenocorticotrophic hormone (ACTH; 100 and 300 U/kg), diphenylhydantoin (15 mg/kg), and phenobarbital (20 mg/kg) and drugs which do not act principally at S2 receptors were ineffective in these models. These data support the hypothesis that myoclonus in behavioral models induced by 5-HT is S2 receptor mediated. S2 antagonists could have a role in the treatment of human myoclonus.
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PMID:Antimyoclonic properties of S2 serotonin receptor antagonists in the rat. 293 77

The protective effect of the precursor of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP) against myoclonus induced in rats by picrotoxin and allylglycine was demonstrated. The inhibition by 5-HTP of picrotoxin-induced myoclonic movements was found to correlate well with an increased 5-HT release from the cerebral cortex. p-Chlorophenylalanine (PCPA) pretreatment aggravated the actions of both picrotoxin and allylglycine by shortening their myoclonic latencies. These findings suggest that there is an antimyoclonic effect of 5-HT in the brain. The protective effect of clonazepam against these two myoclonic models was found to be potentiated in 5-HTP-pretreated animals. Only a partial inhibition of its protective effect resulted from PCPA pretreatment. These data suggest that a beneficial synergism is likely to occur between 5-HTP and clonazepam for the inhibition of myoclonus and that a 5-HTergic mechanism does not play a significant role in the antimyoclonic action of clonazepam.
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PMID:Evidence for synergism between the antimyoclonic actions of 5-hydroxytryptophan and clonazepam in rats. 297 Mar 92

The effects of castration in males and sex differences in the effects of estradiol and progesterone on L-5-hydroxytryptophan (L-5-HTP)-induced myoclonus in guinea pigs were examined. Castration had no effect on L-5-HTP-induced myoclonus in males. There were sex differences in sensitivity to L-5-HTP. In the absence of steroids, L-5-HTP-induced myoclonus was higher in gonadectomized males than females. A low dose of estradiol benzoate (EB; 3.5 micrograms) given 46 h before L-5-HTP (100 mg/kg) enhanced myoclonus in gonadectomized females but not males. However, at a higher dose of EB (10 micrograms) and a lower dose of L-5-HTP (80 mg/kg), myoclonic responding was enhanced in males. These findings indicate that estradiol has a similar effect on L-5-HTP-induced myoclonus in males and females, but do not rule out the possibility of sex differences in sensitivity to L-5-HTP when both sexes are given estradiol priming. When L-5-HTP was given 6 h after 0.5 mg progesterone in estradiol-primed males, myoclonus was enhanced. Progesterone treatment reverses the facilitative effect of EB on L-5-HTP-induced myoclonus in females. Therefore, progesterone has opposite effects on L-5-HTP-induced myoclonus in males and females. These findings were discussed with respect to the interaction of steroids and 5-HT transmission in the regulation of steroid-dependent reproductive behavior.
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PMID:Estradiol and progesterone influence L-5-hydroxytryptophan-induced myoclonus in male guinea pigs: sex differences in serotonin-steroid interactions. 298 88

The acute behavioural consequences of intragastric p,p'-DDT in high doses to mice are stimulus sensitive abrupt muscle jerks (myoclonus). The serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) ameliorated in contrast to the natural precursor tryptophan, the neurotoxin-induced myoclonus. The extracerebral decarboxylase inhibitor carbidopa and the selective 5-HT reuptake inhibitor paroxetine both enhanced the antimyoclonic action of 5-HTP. The effect was reversed by the 5-HT receptor blockers cinanserine and methysergide. The data add further evidence to a central serotonergic mechanism involved in p,p'-DDT induced myoclonus.
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PMID:p,p'-DDT-induced myoclonus in mice: the effect of enhanced 5-HT neurotransmission. 298 13

L-5-Hydroxytryptophan (5-HTP) is a clinically useful antimyoclonic drug that is thought to act at serotonin (5-HT) receptors after decarboxylation to 5-HT. However, the chronic effects of 5-HTP on central 5-HT receptors and the activity of 5-HTP at 5-HT receptor subtypes have not been previously reported. In rats treated 28 but not 7 consecutive days with high doses of 5-HTP (50-200 mg/kg), cortical 5-HT2 (-20%) and 5-HT1 (-11%) sites were downregulated without altered receptor affinity, but only the changes in 5-HT2 sites were significant. In naive frontal cortex in vitro, however, 5-HTP and 5-HT were more active at 5-HT1 sites, and 5-HTP was inactive at 5-HT2 sites. The differential effects of high-dose 5-HTP on 5-HT receptors suggest that 5-HT2 receptor downregulation may be relevant either to the antimyoclonic effect of chronic 5-HTP therapy in posthypoxic myoclonus or to development of tolerance.
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PMID:Effect of chronic treatment with 5-hydroxytryptophan on cortical serotonin receptors in the rat. 326 Nov 99

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


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