Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antihypertensive effects of methyldopa and clonidine result from agonist activity at alpha adrenoceptor sites within the brain. Methyldopa is converted enzymatically to alpha-methylnoradrenaline in noradrenergic neurones in rat brain and replaces the natural transmitter, noradrenaline. Radioligand receptor studies show that alpha-methylnoradrenaline differs from noradrenaline in being much more selective (70 times) for the alpha 2 subclass of adrenoceptors than noradrenaline and it is likely that the antihypertensive action of methyldopa results from selective activation of alpha 2 adrenoceptors by alpha-methylnoradrenaline in the nucleus tractus solitarius and the anterior hypothalamus. Radioligand studies also show that clonidine is a selective alpha 2 adrenoceptor agonist although it probably interacts with alpha 1 adrenoceptors at higher concentrations. With regard to a withdrawal syndrome after cessation of clonidine treatment, the cardiovascular and behavioural components can now be characterised in a rat model. The components include increases in basal blood pressure and heart rate, as well as increases in cardiovascular reactivity and also increases in rapid eye movement (REM) sleep, body shakes and tremor which is reminiscent of an opiate withdrawal syndrome. Increased central noradrenergic activity is involved in this syndrome and alpha 1 and alpha 2 adrenoceptors mediate opposing effects on the REM sleep rebound component.
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PMID:The involvement of central alpha adrenoceptors in the antihypertensive actions of methyldopa and clonidine in the rat. 632 Oct 66

Intrathecal administration of 5,6-dihydroxytryptamine (5,6-DHT) (5 micrograms) to mice selectively lesioned descending serotonergic pathways, reducing spinal levels of 5-hydroxytryptamine (5-HT) by 80%, without significantly changing the levels of noradrenaline. Increased sensitivity to noxious stimulation, as measured by the tail-flick and hot-plate tests, was observed 2 days after injection of 5,6-DHT. The tail-flick latencies returned to normal on day 6, but were again reduced by administration of the 5-HT receptor blocker metergoline, suggesting that the normalization process involved compensatory mechanisms in the remaining 5-HT system. In the hot-plate test, the latencies both to shaking or kicking of a hindpaw (kick) and to hindpaw lick were recorded, but the time course for the changes of these two responses was found to be different. The latencies to hindpaw lick were normalized within 2 weeks, whereas the hindpaw kick latencies remained reduced throughout the 21 day observation period.
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PMID:Changes in nociception after intrathecal administration of 5,6-dihydroxytryptamine in mice. 668 57

The effects of lesioning monoamine pathways in the rat brain on tremorine-induced hind-limb tremor and rigidity were studied. Nigro-striatal and mesolimbic dopamine (DA) neurones were lesioned unilaterally by injecting 6-hydroxydopamine (6-OHDA) into the median forebrain bundle. Tremor was reduced in the contralateral leg and rigidity was prevented in the ipsilateral leg. Injection of 6-OHDA into the nucleus accumbens affected tremor but not rigidity. In general, nigral DA neurones may influence rigidity whilst mesolimbic DA neurones affect tremor. A unilateral locus coeruleus electrolesion which destroys noradrenaline (NA) fibres reduced both tremor and rigidity. A median raphe electrolytic lesion affecting 5-hydroxytryptamine (5-HT) neurones had no effect on tremor and rigidity, whereas lesioning the dorsal raphe electrolytically or by injecting 5,6-dihydroxytryptamine prevented rigidity without affecting tremor. Electrical stimulation of the dorsal raphe increased transiently the hindlimb tone of normal rats. The findings demonstrate that the monoamines, especially 5-HT, are differently involved in the mechanisms of tremor and rigidity produced by tremorine.
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PMID:Effect of lesioning dopamine, noradrenaline and 5-hydroxytryptamine pathways on tremorine-induced tremor and rigidity. 712 51

The hydrochloride salt of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazol hydrochloride (pirlindole) exerts pharmacological effects typical of antidepressants. This compound antagonizes the depressant effects of reserpine and tetrabenazine and potentiates the central effects of amphetamine and l-dopa. It also enhances the head-twitch effect of 5-hydroxy-tryptophan, the effects of noradrenaline, adrenaline, serotonin, tyramine on blood pressure as well as the hypertensive and tremor activities of tryptamine. Pirlindole inhibits the neuronal uptake of noradrenaline and exerts reversible, short-lasting anti-MAO activity. It does not possess anti-cholinergic activity. Clinical trials have shown pirlindole to be effective as an antidepressive drug.
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PMID:Pharmacological properties of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino [3,2,1-j,k]carbazol hydrochloride (pirlindole), a new antidepressant. 719 96

The role of peripheral catecholamines in mediating the pressor and tremorigenic effects of oxotremorine were investigated in conscious rats. At time of peak tremor intensity induced by oxotremorine, plasma adrenaline and noradrenaline were increased 3--4-fold. Tremor intensity was substantially reduced by either adrenal medullectomy, chemical sympathectomy with 6-hydroxydopamine, or injection of 2.5 mg/kg L-propranolol. The pressor response to oxotremorine was not reduced by adrenal denervation, which however prevented the usual rise in plasma adrenaline but not that of noradrenaline. It is concluded that central cholinergic receptor stimulation activates the sympatho-adrenal system. While both adrenaline and intact sympathetic nerves are necessary for the mediation of the full tremorigenic effect, the pressor response to oxotremorine is mainly due to the effect of noradrenaline on vascular alpha-receptors.
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PMID:Peripheral catecholamines mediate certain responses to central cholinergic receptor stimulation by oxotremorine. 723 35

The interrelationships were studied between catecholaminergic and cholinergic systems in 169 patients with extrapyramidal system diseases: 68 patients with torsion dystonia (58 with the rigid form and 10 with the hyperkinetic form), 10 with Hallervorden-Spatz disease, 61 with hepatolenticular degeneration, and in 40 with idiopathic tremor. The secretion of dopamine (DA), noradrenaline (NA), adrenaline (A) and their precursor--DOPA) as well as the activity of acetylcholinesterase (AChe)--the enzyme disintegrating acetylcholine--were determined. In the rigid form of torsion dystonia and in Hallervorden-Spatz disease reduced secretion of all catecholamines (mainly DA) and DOPA was observed, with decreased AChE activity. In the hyperkinetic form of torsion dystonia the secretion of DA was increased and AChE activity was higher. In the patients with idiopathic tremor the secretion of A and NA was decreased and AChE activity was reduced. In patients with hepatolenticular degeneration the secretion of NA and DA was decreased and that of their immediate precursor DOPA was increased. Changes of AChE activity showed a wide range. The observed disturbances reflect various forms of disturbances in the equilibrium between the catecholaminergic and cholinergic systems which are one of the leading pathogenetic mechanisms in the development of various extrapyramidal syndromes.
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PMID:[Characteristics of central neurotransmitter metabolism in hereditary extrapyramidal disorders]. 732 5

A limitation of clonidine therapy is the syndrome of rebound hypertension and sympathetic overactivity after withdrawal. Ten patients, four male, six female, aged 28--64 years, with essential hypertension, were treated for one year with an imidazoline derivative, tiamenidine. Blood pressure fell from an average of 178/108 mm Hg pretreatment to 152/86 mm Hg after 1 year. Tiamenidine was then withdrawn in hospital, replaced by identical placebo under single blind conditions and observations made over 96 h. The study was interrupted in five patients (4 patients within 36 h) because blood pressure rose to greater than 30 mm Hg (systolic) or greater than 20 mm Hg (diastolic) above pretreatment values. For the group, blood pressure was maximal at 194/112 mm Hg, 18 h post withdrawal, significantly higher than pretreatment (p less than 0.005). Headache, tremor, flushing and insomnia were noted. Saliva production rose 100% at 24 h. Plasma noradrenaline rose within 24 h with an accompanying rise in urinary metanephrine and catecholamine excretion. Tiamenidine appears to share with other imidazolines rebound cardiovascular and autonomic effects following abrupt withdrawal.
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PMID:Changes in blood pressure, heart rate, and sympathetic activity on abrupt withdrawal of tiamenidine (HOE 440) in essential hypertension. 746 Oct 12

We postulate that the effect of cholinesterase inhibitors to ameliorate the cholinergic deficit in Alzheimer's disease is related to their ability to maintain long-lasting, non-toxic steady-state levels of acetylcholine in cortex. We investigated the effect of the cholinesterase inhibitor, MDL 73,745 (2,2,2-trifluoro-1-(3-trimethylsilylphenyl)ethanone), on the extracellular levels of acetylcholine, norepinephrine, dopamine and 5-hydroxytryptamine in the cerebral cortex of the rat by high-performance liquid chromatography coupled with electrochemical detection. The drug significantly increased acetylcholine levels above the baseline at 2 and 10 mg/kg s.c., but not at the 1 mg/kg dose. At both 2 and 10 mg/kg there was a good correlation between cholinesterase inhibition and acetylcholine increase in cortex. At the 2 and 10 mg/kg doses, the maximal cholinesterase inhibition was 64% and 77%, respectively, and the increase in acetylcholine release was 481% and 1016%, respectively. Norepinephrine and dopamine, but not 5-hydroxytryptamine levels, were also significantly increased by the 10 mg/kg dose. The increases of norepinephrine and dopamine levels reached a maximum of 124% and 370%, respectively, and continued for a period of at least 8 h. Cholinergic side-effects were most marked at the 10 mg/kg dose but were also noticeable at the 2 mg/kg dose in the form of fasciculations, tremor and splay.
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PMID:Effect of MDL 73,745 on acetylcholine and biogenic amine levels in rat cortex. 778 1

Six healthy males, the EMSInauts, were isolated in hyperbaric chambers for a period of 28 days at 5-msw overpressure. During that period they had to carry out meaningful operational and research tasks in addition to monitoring their psychological and physiological reactions. The actual workload was evaluated and compared with the planned workload, and its effects on symptomatology and psychobiology. The perceived workload and its effects on psychosomatic symptomatology and on some biological indices were monitored. Thus it was possible to evaluate how the workload carried during 4 weeks of isolation affected the psychological and biological well-being of the six EMSInauts. The following three types of assessments were performed: 1. Workload assessment: The objective workload was calculated based on the schedule which was revised daily, and the actual load calculated by the commander. A workload questionnaire was administered daily after each working session. 2. Psychosomatic assessment: Morning and evening questionnaires were administered daily. The state of health and of anxiety were also evaluated. 3. Biological indices: Cortisol, testosterone, adrenalin, and noradrenaline were determined once a week. In addition, cardiac activity was monitored every day. The workload assessment showed that on the average the planned workload was accomplished in slightly less than the scheduled time. The workload was not perceived as severe in terms of cognitive, emotional, and physical load. The group rated the support received from each other and from the mission control personnel as average, with minor changes during the isolation period. They gave a high rating to the amount of control they had over their activities. Fatigue and tension were scored in the middle range. The psychosomatic assessment showed that there were few symptoms, and these were mostly of low severity. The most common symptom was general fatigue. Furthermore, minor dizziness, headache and light tremor was in some cases reported. The sleep quality was good, but complaints about poor sleep increased somewhat with the passing of time. Few and mostly minor health problems were experienced during isolation. Only one EMSInaut had to miss one day of work due to a bout of flu. The state of anxiety was below that of the general population throughout the isolation period. The biological indices used showed no evidence of stress from the workload handled during the isolation period. The level of the "stress hormone" cortisol actually decreased during isolation. The adrenalin excretion, which tends to go up during acute stress, remained unchanged during this period. Neither was there any evidence of changes in cardiac activity throughout the isolation period.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:European isolation and confinement study. Workload and stress: effects on psychosomatic and psychobiological reaction patterns. 816 54

We have studied the developmental time-course of changes in the noradrenaline (NA) content of cerebellum (CE), cytoarchitecture of the cerebellar cortex, and motor abnormalities induced by the exposure of the cephalic end of rats to a single dose (5 Gy) of X-irradiation immediately after birth. At all ages examined, i.e., from postnatal (PN) d 5 to 90, CE from exposed animals show a marked atrophy, with an agranular cortex that has lost its layered structure. Purkinje cells are scattered at all depths in the cortex, and their primary dendrite is randomly oriented. The motor syndrome includes dystonia-like movements, a fine tremor, and an ataxic gait. Being progressive, the abnormal movements are evident from PN d 10, and fully developed by d 30. On the other hand, no differences in cerebellar NA content between X-irradiated rats and age-matched nonirradiated controls were detected from PN d 5 to 60. However, at PN d 90 a significant increase in NA content of CE from exposed animals is found when compared to either age-matched controls (+36%, p < 0.01), or data from irradiated rats obtained at PN d 5 to 60 (p < 0.01). These results indicate a temporal dissociation between the motor and cytoarchitectural abnormalities and the increase in cerebellar NA content produced by a single dose of X-rays at birth. The late increase in cerebellar NA content might represent a compensatory response of noradrenergic terminals to an altered information flow out of the cerebellar cortex induced by the ionizing noxa.
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PMID:Motor abnormalities and changes in the noradrenaline content and the cytoarchitecture of developing cerebellum following X-irradiation at birth. 825 Oct 32


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