Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with severe dementia due to Alzheimer's disease (AD) or multi-infarct dementia (MID) or both, were treated with the precursor amino acids of the neurotransmitters serotonin and dopamine. The precursor amino acids (PAA) were given orally in a preparation that included tyrosine (4 gm daily) and 5-hydroxy-tryptophan (5-HTP) (800 mg daily), plus carbidopa (100 mg daily) as an aromatic amino-acid decarboxylase inhibitor. Diagnosis was established by an electroencephalogram, brain scan, computerized axial tomographic scan, and in one case by necropsy findings. Serial clinical evaluations and measurements of neuropsychologic function were performed. Levels of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) were determined before and after administration of probenecid. Side effects of the PAA therapy were diarrhea, drowsiness, nausea, vomiting and agitation, all of which were controlled by reducing the dosage. One patient with MID and one with AD+MID showed clinical and psychologic improvement, but the others did not improve. Analysis of the cerebrospinal fluid for HVA and 5-HIAA before and after the probenecid test indicated some improvement in the metabolic turnover of these acid metabolites of serotonin and dopamine after administration of their precursor amino acids.
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PMID:Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease. 30 Nov 48

1 The psychotropic effects of a single oral dose of (--)-tryptophan (5 g) in human volunteers were investigated using a series of physiological and psychological tests. 2 Self-ratings of mood showed increase in drowsiness but no euphoria was detected. 3 Severe initial nausea occurred and headache increased; other bodily symptoms were unaffected. 4 Trptophan caused increased activity in the slow wavebands of the EEG but did not alter the other physiological measures. 5 The levels of total and free tryptophan in the plasma increased 8 and 20 fold respectively to peak levels 2 h after ingestion.
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PMID:The acute effects of oral (--)-tryptophan in human subjects. 123 98

The responses of thirteen patients with bulimia nervosa and sixteen controls matched for age and weight are described following the ingestion of a carbohydrate and a calorie-free placebo mixture in simulated binges. Psychological, hormonal and biochemical parameters were measured before and at 15 minute intervals for two hours after the simulated binge. At baseline, the bulimics were clearly more symptomatic than the controls. The control population showed a specific satiating effect of carbohydrate upon hunger ratings. Bulimic patients responded differently showing a blunting of the normal sensation of hunger and an enhanced rating for nausea. Prolactin, growth hormone (GH) and cortisol failed to show a carbohydrate-mediated stimulation in either population. The bulimic patients showed a different pattern of GH release, but this was independent of the challenge condition. Large neutral amino acid (LNAA) levels fell following carbohydrate ingestion, but produced an increase of up to 20% in the tryptophan: LNAA ratio in both bulimic patients and the control group. Thus, while this increase in tryptophan availability failed to provoke hormone release, the time course of the carbohydrate specific effect on the sensations of hunger and nausea is compatible with a mechanism based on increased tryptophan availability. The confusion of satiety with nausea may provide a useful focus for the future treatment of patients with bulimia nervosa.
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PMID:Psychological, hormonal and biochemical changes following carbohydrate bingeing: a placebo controlled study in bulimia nervosa and matched controls. 204 88

A 44-year-old man presented with symptoms of periodic ataxia, dysarthria, nausea and excessive sweating during the last twenty years. These symptoms could be provoked by physical or emotional stress and disappeared after bedrest for several hours. No other members of his family were known to have such complaints. Acetazolamide (Diamox) proved effective in preventing these symptoms. A disturbance of tryptophan metabolism is suggested as a cause of this disorder.
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PMID:Non-familial periodic ataxia responding to acetazolamide. 398 40

Effects of intravenous administration of the serotonin precursor tryptophan (TRP) on serum prolactin, neuromotor function, subjective mood, and blood pressure and pulse were determined in nine depressed patients before and during placebo-controlled treatment with the monoamine oxidase inhibitor (MAOI) tranylcypromine. Tranylcypromine significantly increased the prolactin response to TRP. Four patients developed a distinctive neuromotor syndrome following TRP during tranylcypromine, but not placebo, treatment. Symptoms included hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea. There were no differences in peak prolactin, mood, or autonomic responses between patients with and without the syndrome, but those with the syndrome had received active tranylcypromine for a significantly shorter duration. Tranylcypromine had little effect on TRP-induced changes in mood or autonomic function, except for a modest enhancement of the TRP-induced rise in diastolic blood pressure. These results suggest that tranylcypromine treatment may enhance serotonin function in depression.
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PMID:Effects of tranylcypromine treatment on neuroendocrine, behavioral, and autonomic responses to tryptophan in depressed patients. 403 56

Pain perception and tolerance thresholds of 30 normal subjects were determined by electrical stimulation of dental pulps before and after dietary manipulation which included either tryptophan supplementation or placebo. Perception threshold levels were similar in tryptophan and placebo subjects; however, pain tolerance levels were significantly higher in the group receiving tryptophan. Side effects such as nausea, skin itching, weight loss and mood elevation were more common in the tryptophan group than in the placebo group.
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PMID:Alteration of human pain thresholds by nutritional manipulation and L-tryptophan supplementation. 713 33

We describe a patient treated with trazodone, isocarboxazid, and methylphenidate hydrochloride who developed confusion, agitation, poor concentration, rigidity, myoclonus, involuntary movements, orthostatic hypotension, and hyperreflexia. CK was normal, and the syndrome resolved spontaneously over 12 hours. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan, 3,4-methylenedioxy-methamphetamine, dextromethorphan, meperidine, S-adenosylmethionine) alone or in combination with monoamine oxidase inhibitors. It is characterized by various combinations of myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death.
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PMID:Serotonin syndrome. 785 15

Paroxetine is a novel phenylpiperidine compound that is a potent and selective serotonin reuptake inhibitor. It has little affinity for alpha-adrenergic, dopamine, histamine, and cholinergic receptors. The pharmacokinetic properties of paroxetine are well suited to clinical use. Its bioavailability is not affected by food or antacids; its mean half-life of about 24 hours is consistent with once-a-day dosing; also, it has no pharmacologically active metabolites. In clinical studies involving over 6,700 patients worldwide, the efficacy of paroxetine has been shown consistently to be superior to placebo and comparable to tricyclic antidepressant agents in the treatment of depression. During these trials, paroxetine was used in a broad range of depressed patients, including the moderately to severely depressed, the elderly, and patients whose depressions were accompanied by symptoms of anxiety. In addition, it has been shown to be effective for the prevention of depressive relapse during long-term treatment. Side effects associated with paroxetine tend to be relatively mild, transient, and easily managed. As with other selective serotonin reuptake inhibitors, the most common side effect associated with paroxetine treatment is nausea, although this effect rarely leads to dose reduction or drug discontinuation. Paroxetine should not be coadministered with monoamine oxidase inhibitors or L-tryptophan. Animal data and limited clinical experience suggest that paroxetine is considerably safer in overdose than are tricyclic antidepressant drugs.
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PMID:Paroxetine: an overview of the efficacy and safety of a new selective serotonin reuptake inhibitor in the treatment of depression. 810 49

To assess the possible role of altered central serotonin function in psychiatric disorders, investigators have utilized pharmacological challenge testing with an amino acid mixture to decrease blood tryptophan concentration and, indirectly, brain serotonin levels. The aim of this pilot study was to assess the effectiveness of a modified amino mixture, administered in capsule form, in decreasing plasma tryptophan levels. Studies were conducted in six healthy, medication-free female volunteers. Following double-blind, randomized, cross-over design, subjects received on separate days capsules containing a tryptophan-free amino acid mixture (31.5 grams) or lactose placebo. Over the six hours following amino acid administration, plasma tryptophan concentrations decreased to 21% of baseline values, while the tryptophan/large neutral amino acid ratio decreased to 6% of baseline. Subjects reported minimal symptoms of nausea or other side effects following amino acid administration. The results suggest that the modified amino acid mixture may be useful in assessing behavioral responses to acute tryptophan depletion challenge testing.
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PMID:Comparison of the effects of amino acid mixture and placebo on plasma tryptophan to large neutral amino acid ratio. 884 50

Using the technique of site-directed mutagenesis, point mutants of human PDE4A have been developed in order to identify amino acids involved in inhibitor binding. Relevant amino acids were selected according to a peptidic binding site model for PDE4 inhibitors, which suggests interaction with two tryptophan residues, one histidine and one tyrosine residue, as well as one Zn(2+) ion. Mutations were directed at those tryptophan, histidine, and tyrosine residues, which are conserved among the PDE4 subtypes (PDE4A-D) and lie within the high-affinity 4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram) binding domain of human PDE4A (amino acids 276-681 according to the PDE4A sequence L20965). Truncations to this region do not alter enzyme activity or inhibitor sensitivity. The mutants were expressed in COS1 cells, and the recombinant cyclic nucleotide phosphodiesterase (PDE) forms have been characterized in terms of their catalytic activity and inhibitor sensitivities. Tyrosine residues 432 and 602, as well as histidine 588, were found to be involved in inhibitor binding, but no interaction was detected between tryptophan and PDE inhibitors tested. To test the possibility that other amino acids are of importance for hydrophobic interactions, selected phenylalanine residues were also mutated. We found phenylalanine 613 and 645 to influence inhibitor binding to PDE4. The significant differences in the inhibitor sensitivities of the mutants show that the various inhibitors have different enzyme binding sites. Based on the assumption that the known side effects of PDE4 inhibitors (like emesis and nausea) are caused directly by selective inhibition of different conformation states of PDE4, our results may be a hint to differ between PDE4 inhibitors, which have emetic side effects (like rolipram), and those that do not have side effects (like N-(3,5-dichlorpyrid-4-yl)-[1-(4-fluorbenzyl)-5-hydroxy-indol-3-yl]-glyoxylateamide [AWD12-281]) by the differences of their binding sites and in that context contribute to the development of novel drugs. Furthermore, the identification of amino acid interactions proposed by the peptidic binding site model, which was used for the mutant selection, verifies the PrGen modeling as a useful method for the prediction of inhibitor binding sites in cases where detailed knowledge of the protein structure is not available.
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PMID:Identification of inhibitor binding sites of the cAMP-specific phosphodiesterase 4. 1130 46


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