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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain serotonin (5-hydroxytryptamine, 5-HT) has been suggested to be involved in central fatigue during prolonged exercise. Changes in the ratio of plasma free tryptophan (free Trp) to branched-chain amino acids (BCAA) are associated with altered brain 5-HT synthesis. The purposes of this study were to describe systematically the effects of prolonged exercise on changes in plasma free Trp and BCAA and to examine the effects of carbohydrate (CHO) feedings on these same variables. Eight well-trained men [VO2max = 57.8 (SE 4.1) ml kg-1 min-1] cycled for up to 255 min at a power output corresponding to VO2 at lactate threshold (approximately 68% VO2max) on three occasions separated by at least 1 week. Subjects drank 5 ml kg-1 body wt-1 of either a water placebo, or a liquid beverage containing a moderate (6% CHO) or high (12% CHO) concentration of carbohydrate beginning at min 14 of exercise and every 30 min thereafter. Exercise time to fatigue was shorter in subjects receiving placebo [190 (SE 4) min] as compared to 6% CHO [235 (SE 10) min] and 12% CHO [234 (SE 9) min] (P < 0.05). Glucose and insulin decreased in the placebo group, and free Trp, free-Trp/BCAA, and free fatty acids increased approximately five- to sevenfold (P < 0.05). These changes were attenuated in a dose-related manner by the carbohydrate drinks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of carbohydrate feedings on plasma free tryptophan and branched-chain amino acids during prolonged cycling. 148 39

The present paper reviews evidence for the role of specific amino acids in the etiology of fatigue and the overtraining syndrome in athletes. An increase in the plasma concentration ratio of free tryptophan: branched-chain amino acids may mediate an increase in 5-HT synthesis in the brain and thus induce fatigue during exercise. Glutamine is essential for the proper functioning of cells of the immune system and a decrease in plasma glutamine concentration post-exercise and in overtraining may induce an impairment in immune function. Branched-chain amino acids may play a central role in both these processes. Thus, they compete with free tryptophan for entry into the brain. Branched-chain amino acids may also be important precursors of nitrogen for the synthesis of glutamine in skeletal muscle or important in the control of glutamine release from muscle. Consequently, the metabolism of glutamine, tryptophan, and branched-chain amino acids may be the key to understanding some aspects of central fatigue and some aspects of immunosuppression that are very relevant to athletic endeavor. They may be also relevant to other physiological and pathological conditions.
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PMID:A communicational link between skeletal muscle, brain, and cells of the immune system. 219 90

This study investigates, both behaviourally and biochemically, the action of 2-allophanyl-2-allyl-4-valerolactone (Valofan) in the mouse, after acute or repeated administration. The exploratory behaviour was measured in different experimental conditions by a hole-board test modified in observation length: 10 min instead of original 5. The variations in 5-HT and 5-HIAA levels were measured in cortex and brainstem. Acute administration of Valofan (50 to 500 mg/kg os) did not change exploration during the first 5 min period, while at higher doses (200-500 mg/kg) it did produce a significant increase in basal exploratory behaviour, measured by prolonging hole-board test to 10 min. These data were confirmed by the habituation test to he thole-board whereby, after three days of exposure, low exploratory baseline of mice was constant. The elevation of the exploration was consistant with a significant net increase in 5-HT levels (greater than 5-HT; less than 5-HIAA) in brainstem, and with a relative enhance in amine levels (= 5-HT; less than 5-HIAA) in cortex for higher doses of the drug. Modifications of serotonin mechanisms positively affect behaviour in an unfamiliar environment. Surprisingly repeated treatment (for 8 days) with Valofan did not change exploration in respect of controls. The biochemical pattern of repeated treatments showed that higher doses of drug increased 5-HT without affecting 5-HIAA levels in brainstem and cortex. Repeatedly handheld mice showed control values significantly higher than those of acute treatment. This increase in activity corresponded to a biochemical pattern similar to that obtained after acute administration of 500 mg/kg Valofan, indicating that handling affected the basal 5-HT content. Thus Valofan could stimulate exploration in mice with a low baseline, while it did not change the activity of animals with a higher baseline. Further evidence for a possible involvement of 5-HT mechanisms in the action of Valofan was given by the fatigue test. Mice, submitted to hole-board after 24 h of forced walking, showed, with 500 mg/kg, a significant decrease in exploration: action of Valofan seemed to potentiate the effects exerted by stress on serotonin turnover.
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PMID:Effect of an atypical barbiturate, the 2-allophanyl-2-allyl-4-valerolactone (valofan), on exploratory behaviour and brain serotonin concentrations in mice. 241 78

Fluoxetine, a selective inhibitor of 5-HT uptake, was compared to dothiepin in a double-blind study of 6 weeks duration in 100 depressed patients (male and female) drawn from 8 general practices. Only those who scored at least 17 on the first 17 questions of the Hamilton Psychiatric Rating Scale for Depression (HAM-D) were selected. Both groups improved throughout the trial, though the dothiepin treated patients tended to improve quicker. However, by the end of the trial there was no statistically significant difference between the 2 groups. Subset analyses of HAM-D scores associated with anxiety and sleep revealed no statistically significant differences between the 2 treatments though improvement in anxiety scores was marginally greater for those receiving fluoxetine by the end of the trial. Other global assessments by patients and doctors confirmed the changes in HAM-D scores. Statistically significant weight changes occurred between visits 1 and 5. Whereas fluoxetine-treated patients lost weight (p less than 0.05), dothiepin-treated patients gained weight (p = 0.05) over this period. Adverse effects were reported in 27 patients given fluoxetine and 20 dothiepin. Of these, 14 fluoxetine and 7 dothiepin-treated patients withdrew before the end of the trial. The most common adverse effects were nausea, vomiting and diarrhoea in the fluoxetine group and tiredness, drowsiness and diarrhoea in the dothiepin group. There were no haematological or clinical chemistry changes.
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PMID:A double-blind comparative study of fluoxetine and dothiepin in the treatment of depression in general practice. 267 26

The hypotheses that defective platelet structure and function is the basis for migraines is presented, with evidence explaining the biochemical, clinical, pathological, and pharmacological aspects of migraine. Platelets undergo 2 types of reaction, a shape change and a granule release reaction, releasing adenosine diphosphate (ADP) serotonin 5-hydroxy-tryptamine (5-HT), and thromboglobulin in response to collagen and thrombin. Platelets from migraine suffers contain more ADP, have more dense granules, and show some qualitative differences in their release reaction. Their platelets aggregate more readily when exposed to 5-HT, their platelet fibrinogen receptors have greater affinity, and their platelet membranes show altered viscosity. Some drugs that inhibit platelet aggregation, such as methysergide, aspirin, and amitryptylline, are beneficial in cases of migraine. Some migraine triggers, such as tyramine and catecholamines, are known to be vasoactive. The release by platelets of 5-HT may account for the visual aura or prodrome that migraine patients experience. Some migraine precipitating factors, such as stress, fatigue, hunger, certain foods, and hormones, may stimulate 5-HT release by platelets. Alterations in hormones, notably puberty, menstruation, oral contraceptive use, and menopause, are characterized by altered platelet aggregation and by onset of migraine in previously healthy people. Other arguments in favor of the platelet hypothesis involve prostacyclin deficit during menstruation and migraine associated with sudden decline in platelet numbers in cases of thrombocytopenic purpura and essential thrombocythemia.
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PMID:Migraine: the platelet hypothesis after 10 years. 270 Dec 86

beta-Adrenoreceptor antagonists are liable to produce behavioural side-effects such as drowsiness, fatigue, lethargy, sleep disorders, nightmares, depressive moods, and hallucinations. These undesirable actions indicate that beta-blockers affect not only peripheral autonomic activity but also some central nervous mechanisms. In experimental animals beta-blockers have been found to reduce spontaneous motor activity, to counteract isolation-, lesion-, stimulation- and amphetamine-induced hyperactivity, and to produce slow-wave and paradoxical sleep disturbances. Furthermore, central effects such as tranquilizing influences are used for the treatment of conditions such as anxiety. Several different mechanisms of action could be responsible for these CNS effects: Centrally mediated specific actions on centrally located beta-adrenergic receptors, known to exist downstream from, and at the terminals of, 'vigilance-enhancing' central noradrenergic pathways. Centrally mediated specific actions on centrally located receptors of the non-adrenergic type; an affinity of some beta-blockers towards 5-HT-receptors is well documented. Centrally mediated non-specific actions on centrally located neurones, owing to the membrane-stabilizing effects of beta-blockers. Peripherally mediated actions whereby beta-blockers induce changes in the autonomic activity in the periphery, which are relayed to the CNS to induce changes in activity of a variety of central systems. It can be assumed that with any one of the beta-blockers all these mechanisms come into play, yet with varying degrees depending on characteristics of the drugs such as lipophilicity and hydrophilicity, the ratio of antagonist versus (partial) agonist properties, affinity to 'alien' receptor sites, strength of membrane-stabilizing activity, stereospecific affinity, and potency.
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PMID:CNS-related (side-)effects of beta-blockers with special reference to mechanisms of action. 286 51

Behavioral, physiologic and exertional fatigue is differently defined, though symptoms are similar. The beneficial effect of amantadine on fatiguability in multiple sclerosis is accompanied by neuropeptide and lactate changes in the circulation. Exercise sometimes overwhelms temperature regulating mechanisms and may be associated with heat stroke. Endogenous opioids are markedly increased in the circulation during heat stroke and the use of specific opioid antagonists therapeutically has been proposed for heat stroke. Sympathetic activity changes in endurance trained subjects and vasoconstrictor responses are markedly attenuated. Similar changes occur in parasympathetic function which can be abnormal in up to 90% of endurance trained subjects. Hormonal secretion during prolonged exertion is altered and the normal signals (inhibiting or activating feedback mechanisms) are different in endurance trained subjects. Altitude, associated with acute mountain sickness, is also accompanied by an increase in cranial bloodflow. Circadian and temporal variation in autonomic function are manifest by changes in mast cell numbers and 5-HT containing nerve fibers in temple skin of patients with cluster headache. The remission rate induced by vagal stimulation in subjects with intractable hiccups is also affected by circadian hormonal or neurogenic influences.
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PMID:The autonomic nervous system and fatigue. 296 78

Citalopram, a selective 5-HT uptake inhibitor with antidepressant properties, was assessed in three studies in 12 healthy subjects using a battery of EEG, psychological, subjective and symptomatic measures. Study A involved the administration of citalopram, 20 mg and 40 mg, amitriptyline 50 mg and placebo in single dose using a balanced cross-over design. The test battery was applied before, and 1 and 3 h after each drug. Citalopram decreased slow-wave EEG activity whereas amitriptyline increased power in most EEG wavebands. Citalopram increased tapping rate and symbol copying whereas amitriptyline impaired these and other psychomotor tasks. Subjectively, amitriptyline was much more sedative than citalopram and produced more complaints of dry mouth. Study B comprised the administration of citalopram in the usual clinical dose of 40 mg, amitriptyline in the low clinical dose of 75 mg and placebo, each given for 9 nights using a balanced cross-over design. The test battery was applied on the first morning (pre-drug) and on the morning after the last nightly dose. None of the physiological tests showed any drug effects. Subjectively, citalopram was associated with feelings of shaking, nausea, loss of appetite and physical tiredness; amitriptyline produced feelings of shaking, nausea, loss of appetite, dryness of mouth, irritability, dizziness and indigestion; in general, amitriptyline effects were more marked than those of citalopram. Plasma samples were taken on the last day and plasma concentrations of both drugs and their metabolites were found to be in the expected range for the regimens used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of citalopram in single and repeated doses and with alcohol on physiological and psychological measures in healthy subjects. 346 75

Hungry leeches, Hirudo medicinalis, ingest blood meals averaging 890% of their mass in 29 min. Ingestion is terminated as a result of distension of the body: experimentally distending leeches as they feed causes an immediate cessation of ingestion and inhibits any subsequent biting behaviour; if distension is circumvented by various experimental procedures, leech ingestive periods are prolonged significantly. Ingestion is not terminated as a result of fatigue, chemical cues or mass change. Distension also underlies satiation, for removing blood from the crops of recently fed leeches qualitatively alters their satiated behaviour to biting. Biting is not a defensive reaction to injury. In rostral ganglia, impulses of the serotonergic Retzius (RZ) and LL neurones evoke the physiological components of ingestion. Localized warming of the prostomial lip induces impulses in these large effector neurones. Distending the body wall tonically hyperpolarizes the RZ and LL cells. This inhibitory response to distension is conducted from the mid-body to the anterior neurones via the ventral nerve cord. Distensive inhibition antagonizes the synaptic excitation evoked in RZ and LL neurones by thermal stimulation. Thus, a stimulus which evokes feeding synaptically excites 5-HT neurones and a stimulus which terminates ingestion inhibits them. The integration of these inputs controls the expression of leech feeding behaviour and these connections match precisely a model proposed to regulate the ingestive behaviour of blowflies.
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PMID:On the termination of ingestive behaviour by the medicinal leech. 369 11

In a double-blind placebo-controlled study, the encephalotropic, psychotropic, pharmacodynamic and pharmacokinetic properties of 2 new substances, clovoxamine (a 5-HT and NE re-uptake inhibitor) and fluvoxamine (a selective 5-HT inhibitor) were investigated utilizing quantitative pharmaco-EEG, psychometric and blood level analyses. Ten normal volunteers received randomized and in weekly intervals oral single doses 50 mg, 75 mg and 125 mg clovoxamine, 75 mg fluvoxamine, placebo and as reference drug 75 mg imipramine. Quantitative EEG, psychometric data, pulse, blood pressure, side effects and pharmacokinetic data were studied at the hours 0, 2, 4, 6 and 8. Plasma levels of both substances peaked in the 4th to 6th hour and declined slowly thereafter. Digital computer period analysis of the EEG demonstrated after clovoxamine only minor changes characterized by an increase of fast beta-activities suggesting slight activating qualities of the drug. On the other hand 75 mg fluvoxamine and especially 75 mg imipramine produced marked CNS changes characterized by a concomitant increase of slow and fast activities and a decrease of alpha-activity. However, 75 mg fluvoxamine induced less augmentation of slow activity than imipramine indicating less sedative properties of fluvoxamine than the standard reference drug. Psychometric tests demonstrated after 50 and 75 mg clovoxamine and 75 mg fluvoxamine an increase in attention, attention variability, concentration, CFF and after-effect in the Archimedean Spiral (indicating central activation), further an improvement in mood and affectivity as compared with placebo, while 125 mg clovoxamine and 75 mg imipramine produced an increase in reaction time, deterioration of mood and affect and psychomotor activity. The latter changes were observed also after other antidepressants in normals. Pharmacodynamic investigations regarding dose-efficacy and time-efficacy relations based on both EEG and psychometric parameters revealed that 75 mg imipramine was the most effective compound, followed by 75 mg fluvoxamine and 125 mg, 75 mg and 50 mg clovoxamine. The peak effect of clovoxamine and fluvoxamine was observed around the 6th hour, while 75 mg imipramine was maximally observed around the 6th hour, while 75 mg imipramine was maximally effective between the 2nd and the 4th hours. Side effects were minimal after clovoxamine (interestingly euphoria in 3 subjects), while tiredness was seen in 5 out of 10 subjects after 75 mg fluvoxamine and in 8 out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.
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PMID:Clovoxamine and fluvoxamine-2 biogenic amine re-uptake inhibiting antidepressants: quantitative EEG, psychometric and pharmacokinetic studies in man. 677 58


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