Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of 5-hydroxytryptamine (5-HT) on the release of acetylcholine (ACh) from the brain of the guinea-pig was investigated in order to determine whether this amine plays a modulatory role on the cortical cholinergic projections. 5-Hydroxytryptamine (0.2-1 mumol), injected intracerebroventricularly (i.c.v.), caused mild excitation, stereotyped movements and ataxia. Simultaneously, it increased the output of ACh from the cortex in a dose-dependent manner. Methysergide (4.2 mumol Kg-1 i.p.) also increased the output of ACh by about 60-80%, but prevented the effect of 5-HT (1 mumol i.c.v.). Metitepine (1-4.2 mumol kg-1 i.p.) increased the output of ACh like methysergide but it changed the facilitation of the release of ACh by 5-HT into inhibition. At the same time the animals became hypothermic, sedated and their electroencephalogram (EEG) was synchronized. Pretreatment with 5,7-HT blocked the increase in release of ACh produced by 5-HT (1 mumol). D-Norfenfluramine (10.4 mumol kg-1) was ineffective alone but reduced the release of ACh in metitepine-pretreated animals. 5-Hydroxytryptamine (10-30 microM) did not affect the efflux of [3H]choline from electrically-stimulated slices of cerebral cortex. The increase in the release of ACh caused by 5-HT, abolished by pretreatment with methysergide and 5,7-HT, may be explained by activation of 5-HT autoreceptors, while the increase of transmitter outflow induced by methysergide may be due to a blockade of 5-HT receptors present on the cholinergic neurones. Metitepine appeared to unmask the tryptaminergic inhibition caused by injection of 5-HT intraventricularly or by the 5-HT-releasing drug, D-norfenfluramine, possibly by acting on the autoreceptors and preventing auto-inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of 5-hydroxytryptamine on the release of acetylcholine from guinea-pig brain ex vivo and in vitro. 294 99

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