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

Purpose of this study was to evaluate the activity of dihydroergocristine (DHEC, CAS 17479-19-5) at three different dosages, when administered to aged patients with senile dementia of Alzheimer type. Eighty patients, 48 males and 32 females, aged 55-80 years, affected with senile organic brain syndrome, were admitted to the trial. Clinical evaluation was made by SCAG (Sandoz Clinical Assessment Geriatric Scale). Inclusion criteria considered patients presenting at the basal evaluation a total SCAG score between 60 and 90, with stressed impairment of cognitive function. All the patients were divided in four groups and treated with DHEC 1.5, 3, 6 mg/d or placebo for three months. The evaluation of the total SCAG score demonstrated a significant activity of the drug compared vs placebo, and a dose-related effect. Also for the single clusters it was demonstrated a significant (p < 0.05) dose/effect relation, except for the "affective" one; on the contrary "cognitive functioning" cluster displayed the best benefit. The drug was very well tolerated, as only some cases of dyspepsia, mild gastralgia and nausea were reported in some patients.
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PMID:[Dihydroergocristine in the treatment of organic brain psychosyndrome. Dose-finding study against placebo]. 149 61

Selegiline, an inhibitor of monoamine oxidase B, was tested on patients with mild to moderate dementia of the Alzheimer type. Its efficacy and tolerability were compared with that of phosphatidylserine in a randomized, single-blind, parallel fashion. Forty patients (24 men and 16 women) entered the trial. Selegiline was administered in 10-mg tablets once daily and phosphatidylserine in 100-mg capsules twice daily, both treatments lasting three months. Drug efficacy was assessed at baseline and then each month by means of an extensive battery of neuropsychological tests. The assessment of drug safety was based on monitoring for adverse drug reactions and on routine laboratory tests performed before and after treatment. At the end of the study the selegiline group showed improvements statistically significantly superior to those obtained in the phosphatidylserine group on most of the cognitive areas examined. Furthermore, of particular interest was the discovery, found only in the selegiline group, of an increased degree of autonomy in day-to-day activities. Tolerability was good, the only side effect reported in both groups being slight or moderate nausea, which was severe enough to warrant withdrawal from treatment only in one case, a patient in the selegiline group with a history of gastroduodenitis.
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PMID:Selegiline in the treatment of mild to moderate Alzheimer-type dementia. 212 60

A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the acetyl-l-carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.
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PMID:Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia. 217 69

Deferoxamine treatment may produce serious side effects that can be eliminated by modification of treatment and by control of deferoxamine metabolism. A patient suffering from dementia of the Alzheimer type with normal liver and kidney function who was treated with deferoxamine initially tolerated a dose of 7 mg/kg deferoxamine mesylate injected intramuscularly twice a day for a total of 5 days a week. After several months nausea and weight loss gradually developed in the patient that could be controlled initially by dose reduction, leading to levels inappropriate for aluminum chelation. HPLC analysis of blood and urine revealed several metabolites including, as a major component, a plasma monoamine oxidase (MAO) catalyzed end product MFO1. Coadministration of isoniazid, a plasma MAO inhibitor, with deferoxamine resulted in reduction of MFO1 from 81% to 8% accompanied by increases in the amounts of metabolite 2 (MFO2) from 2% to 24% and unmetabolized deferoxamine from 17% to 68% after 6 months of treatment. The side effects subsided, the patient regained weight, and treatment could be continued.
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PMID:Suppression of deferoxamine mesylate treatment-induced side effects by coadministration of isoniazid in a patient with Alzheimer's disease subject to aluminum removal by ionspecific chelation. 222 4

HP 029 (1,2,3,4-tetrahydro-9-aminoacridin-1-oL-maleate), an oral anticholinesterase, enhances memory in rodents and may be useful in treating Alzheimer's disease (AD). To assess adverse events in relation to dosage and plasma drug levels, 24 hospitalized AD subjects were randomly assigned to receive placebo or HP 029 for 10 days in a double-blind, sequential escalation study. Maximum daily dosages were 450 mg (group 1), 300 mg (group 2), and 225 mg (group 3), divided into three doses per day. The group 1 trial was discontinued on day 5 because one subject, 6 hours following the second of three scheduled 150-mg doses, had a tonic seizure after protracted vomiting and hyperventilation; adverse events in other patients included nausea, vomiting, abdominal cramps, diarrhea, dizziness, and syncope. Adverse events were generally less severe in group 2, but only two of six HP 029 subjects could complete the trial at 300 mg/day. All group 3 subjects completed the trial at 225 mg/day with drug related, mild adverse events (nausea, vomiting, lacrimation, rhinorrhea) in only two subjects. Although mean plasma drug levels were related to adverse events across dosage groups, they did not adequately predict the occurrence or severity of adverse events in individual subjects. The 225 mg/day dose appears to be safe for use in multicenter outpatient trials of HP 029 efficacy in AD. Further patient studies are ongoing to determine the relation of specific subject characteristics to the metabolic profile of HP 029 and biological response.
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PMID:Clinical safety, tolerance, and plasma levels of the oral anticholinesterase 1,2,3,4-tetrahydro-9-aminoacridin-1-oL-maleate (HP 029) in Alzheimer's disease: preliminary findings. 235 6

To assess central nervous system cholinergic neuroendocrine regulation in Alzheimer's disease (AD), we measured plasma arginine vasopressin, beta-endorphin, and epinephrine responses to a cholinergic challenge elicited by intravenous administration of the acetylcholinesterase inhibitor physostigmine (0.0125 mg/kg) in male patients with AD (n = 12) and compared their responses with those of age-matched normal control subjects (n = 12). Physostigmine promptly increased plasma arginine vasopressin (tenfold), beta-endorphin (twofold to threefold) and epinephrine (threefold) levels in elderly control subjects. In contrast, patients with AD showed attenuated responses to physostigmine. When controls and patients with AD who experienced nausea (n = 2 and n = 6, respectively) were excluded, the arginine vasopressin, beta-endorphin, and epinephrine responses of patients with AD were significantly less than those of control subjects. These data suggest that the central nervous system cholinergic deterioration of AD results in decreased responsiveness of neuroendocrine systems that are regulated by central cholinergic mechanisms.
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PMID:Neuroendocrine responses to physostigmine in Alzheimer's disease. 252 15

After a decade of intense study of cholinergic therapies for Alzheimer's disease, three conditions in this field are apparent: 1) The potential that cholinergic agents will ameliorate the memory dysfunction of Alzheimer patients (as 1-dopa benefits Parkinson patients) is still a stimulus for research. 2) Cholinergic neuropharmacology and its impact on the therapy of memory disorders associated with cholinergic dysfunction needs to be further characterized and understood. 3) While there is still a search for a symptomatic treatment for AD, the path to find a treatment for the Alzheimer disease process must first pass through a phase of basic research to find the cause of Alzheimer's disease. At the meeting, there was an undercurrent of concern that the cholinergic deficit is too severe to be treated, that the cholinergic systems are too complex to respond to a pharmacologic therapy and that too many other systems are involved in Alzheimer's disease for a cholinergic treatment to be successful. However, this concern was balanced by the evidence of basic scientific experiments which indicate that the central cholinergic system mediating memory can be positively manipulated in animal lesion preparations and Alzheimer tissue. Also there were reports that improved pharmacological approaches and psychological measures are being developed. It appears that Alzheimer therapy is at the stage that cancer chemotherapy was 20 years ago: the promising agents cause nausea without producing clear effects but the basic laboratory studies strongly suggest that substantial benefits are possible and several agents have shown encouraging results. Meanwhile, patients and scientists are becoming increasingly interested in the field.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Advances in Alzheimer therapy: cholinesterase inhibitors. 275 60

CI-979 ((E)-1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxaldehyde, O-methyloxime monohydrochloride), a novel muscarinic agonist, is being investigated as a potential treatment for Alzheimer's disease (AD). The objective of the present study was to determine the safety and tolerance of multiple, rising, oral doses of CI-979 in patients with AD. Ten male patients aged 59 to 74 years (mean 65 years) who met NINCDS criteria for AD were randomized to receive either CI-979 (eight patients) or placebo (two patients) according to a double-blind, parallel-group, rising-dose design. Doses were 0.5-mg q6h, 1-mg q12h, 1-mg q6h, 2-mg q12h, 2-mg q6h, 2.5-mg q6h, and 3-mg q6h. All doses were to be administered sequentially for 3 days each with the exception of the 2.5-mg q6h dose, which was to be administered for 1.5 days. Five patients receiving CI-979 discontinued study medication because of adverse events; two after receiving 2-mg q6h (10 doses), two after 2.5-mg q6h (5 doses), and one after 3-mg q6h (4 doses). The study was terminated following administration of the fourth 3-mg dose due to the nature and intensity of adverse events. Cholinergic symptoms including diaphoresis, hypersalivation, nausea, diarrhea, hypotension, chills, headache, flatulence, and urinary frequency and signs suggestive of parkinsonism (cogwheeling, tremor, pillrolling, posturing, and shuffling gait) were dose-limiting. The frequency and intensity of adverse events increased with increasing CI-979 dose. No other clinically significant CI-979-related changes occurred in physical examinations, clinical laboratory measurements, electrocardiograms, or ophthalmologic examinations. Steady-state trough plasma CI-979 concentrations increased in proportion to dose. In summary, CI-979 doses of 1-mg q6h were well tolerated by all patients; 2-mg q6h was tolerated by most patients, and 2.5-mg and 3-mg doses were poorly tolerated, Dose titration to a maximum of 2-mg q6h will therefore be used in initial efficacy trials of CI-979 in patients with AD.
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PMID:Safety and tolerability of CI-979 in patients with Alzheimer's disease. 762 16

Alzheimer's disease (AD) is a central nervous system disorder characterized by the presence of neurofibrillary tangles, neuritic plaques and dystrophic neurones in susceptible areas of the brain. Few options for treatment of AD symptomatology are available. We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel trial consisting of a 90 day treatment period followed by a 30 day single blind placebo administration and by an optional long term period of treatment up to a year with idebenone in open fashion. Ninety two patients entered the study and nine of them dropped out before the first control. Treatment with idebenone was found effective on memory, attention, and orientation and in slowing down the natural progressive worsening of the disease. The most common side effects associated with this treatment were insomnia, gastralgia, nausea, and anxiety. However, all adverse effects were of mild intensity and did not require specific therapies.
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PMID:Idebenone, a new drug in the treatment of cognitive impairment in patients with dementia of the Alzheimer type. 798 44


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