Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacology, pharmacokinetics, efficacy, and adverse effects of dexfenfluramine hydrochloride are reviewed. Dexfenfluramine, the dextrorotatory isomer of fenfluramine, is indicated for use in the management of obesity in patients with a body mass index of > or = 30 kg/m2, or > or = 27 kg/m2 in the presence of other risk factors. Unlike fenfluramine, dexfenfluramine is a pure serotonin agonist. Dexfenfluramine may mimic the effect of carbohydrate intake. Systemic bioavailability is about 68%, and the drug is metabolized in the liver. In randomized, placebo-controlled trials, dexfenfluramine was effective in reducing weight in obese patients given the drug for three or six months. In trials lasting one year, the statistically significant weight loss occurred during months 4 to 6. Dexfenfluramine reduces blood pressure, percent glycosylated hemoglobin, and concentrations of blood glucose and blood lipids, but these benefits may be indirect. Dexfenfluramine may also be of some value in controlling eating habits in diabetic patients, preventing weight gain after smoking cessation, and treating bulimia, seasonal affective disorder, neuroleptic-induced obesity, and premenstrual syndrome. Dexfenfluramine's most frequent adverse effects are insomnia, diarrhea, and headache; it has also been associated with primary pulmonary hypertension. The drug should not be combined with other serotonergic agonists because of the risk of serotonin syndrome. The recommended dosage is 15 mg twice daily. Dexfenfluramine is effective in the treatment of obesity in selected patients. Because its efficacy is lost after six months of continuous treatment, it should be viewed primarily as an adjunct to diet and exercise.
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PMID:Dexfenfluramine hydrochloride: an anorexigenic agent. 937 5

Despite the fact that melatonin has been released for public use in the United States by the Food and Drug Administration and is available over the counter nationwide, there currently is a total lack of information on the toxicology of melatonin. In Europe, melatonin has a completely different status in that it is considered a "neurohormone" and cannot be sold over the counter. Even though administration of melatonin in humans, as well as in animals (even at supraphysiological doses), has not shown evidence of toxicological effects (i.e., no deaths), a drug toxicological file still would need to be prepared and approved by the regulatory authorities. Several features that are specific to this neurohormone need to be taken into consideration. Whatever the species concerned, melatonin is secreted during the night; it is the "hormone of darkness." It presents a circadian rhythm and a circannual rhythm (in photoperiodic species). The duration of these secretions could have an impact on the reproductive system, for example, showing the importance of the pharmacodynamics of melatonin. An inappropriate time schedule of melatonin administration could induce supraphysiological concentrations of the neurohormone and a desensitization of melatonin receptors. A long duration of exposure to melatonin also could mimic an "artificial darkness" condition when a circadian rhythm with a basal zero level during the day needs to be conserved for a physiological function. Furthermore, administration of large doses of melatonin could induce high concentrations of melatonin and of different metabolites that could have deleterious effects per se. Numerous books, magazines, and articles have praised melatonin as a "miraculous cure-all" for ailments ranging from sleeplessness, to aging, without any clinical evidence of efficacy (with the exception of its chronobiotic and resynchronizing effect). Very little attention has been paid to the possible side effects of melatonin. Nightmares, hypotension, sleep disorders, abdominal pain, etcetera, have been reported. In fact, analysis of the known pharmacological profile of melatonin and/or of its metabolites, based on scientific preclinical studies, constitutes a basis for prediction of adverse drug reactions or side effects. These include (1) the central nervous system, (2) the cardiovascular system and platelet aggregation, (3) glucose metabolism, (4) immunology, and (5) cancer. The knowledge of the fundamental mechanism of action of melatonin, including molecular biology, also needs to be taken into account for evaluation of possible side effects. Two types of melatonin receptors have been cloned (related to cyclic AMP), and the possibility of intracellular action of melatonin cannot be excluded. Melatonin receptors are present in the periphery and also at the level of the central nervous system, particularly on the suprachiasmatic nucleus that "drives" a circadian rhythm to many other areas on which it projects. Among those, the hypothalamus (which has melatonin receptors) plays a fundamental role in the hormonal homeostasis and modulation control of the organism. Special preclinical and pharmacological studies that take into account all these parameters need to be designed for safety evaluation and risk assessment of this specific neurohormone.
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PMID:Toxicology of melatonin. 940 48

Central nervous system complications are common in stem cell transplant recipients, but selective involvement of the medial temporal area is unusual. The 5 patients reported here presented after stem cell transplantation with increased hippocampal T2 signal on magnetic resonance imaging and increased hippocampal glucose uptake on [F-18]fluorodeoxyglucose-positron emission tomography (FDG-PET) associated with short-term memory loss, insomnia, and temporal lobe electrographic seizure activity. The initial scalp electroencephalograms (EEGs) failed to detect seizure activity in these patients, although the memory dysfunction along with the magnetic resonance imaging and FDG-PET findings suggested subcortical seizure activity. However, extended EEG monitoring revealed repetitive temporal lobe electrographic seizure activity. Follow-up MRIs in 2 patients and postmortem findings on 1 patient suggested that hippocampal sclerosis had developed following the clinical syndrome. Cerebrospinal fluid studies revealed the presence of human herpesvirus 6, variant B, DNA in all of 3 patients who had lumbar punctures. Immunohistochemical staining for the P41 and P101 human herpesvirus 6 protein antigens showed numerous immunoreactive astrocytes and neurons in the hippocampus of 1 of the patients who died from other causes. Because of its subtle clinical presentation, this syndrome may be underrecognized, but can be diagnosed with appropriate magnetic resonance imaging techniques, EEG monitoring, and cerebrospinal fluid viral studies.
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PMID:Human herpesvirus 6 limbic encephalitis after stem cell transplantation. 1170 67

Sibutramine is a combined serotonin(5-HT) and noradrenaline (NA)re-uptake inhibitor. Sibutramine works predominantly through its two pharmacologically active metabolites (i.e. primary and secondary amines) which induce marked weight loss by affecting both food intake and energy expenditure. It is able to enhance the physiological process of satiety, and to stimulate thermogenesis, increasing the efferent sympathetic activity to thermogenically active brown fat. There is a dose-related reduction in body weight in clinical trials with sibutramine, with weight loss up to 11% below baseline, which can last up to 18 months with continued treatment. When weight loss is induced with a very low calorie diet (VLCDL), patients randomized to the sibutramine treatment continued to lose weight over a 1 year period, reaching 15% below baseline, whereas the placebo-treated patients regained some weight. Sibutramine improves metabolic fitness, by decreasing the biochemical risk factors associated with obesity, such as plasma triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol, glucose and insulin, and increasing HDL-cholesterol. In controlled studies, 84% of sibutramine-treated patients reported side effects, most commonly including dry mouth, constipation and insomnia, compared with 71% of patients receiving placebo. A small increase in heart rate and blood pressure also occurs and persists for as long as treatment is continued, which, therefore, requires monitoring. Nevertheless, successful treatment of moderately hypertensive obese patients with sibutramine has been demonstrated without undue blood pressure problems and even a mean lowering of blood pressure associated with weight loss. Finally, sibutramine does not have the potential for abuse that is characteristic of amphetamine and it is indistinguishable from placebo in abuse potential studies.
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PMID:An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action. 1211 86

Knowing how and when the degenerative process starts is important in neurodegenerative diseases. We have addressed this issue in fatal familial insomnia (FFI) measuring the cerebral metabolic rate of glucose (CMRglc) with 2-[18F]fluoro-2-deoxy-D-glucose PET in parallel with detailed clinical, neuropsychological examinations and polysomnography with EEG spectral analyses. Nine asymptomatic carriers of the D178N mutation, 10 non-carriers belonging to the same family, and 19 age-matched controls were studied over several years. The CMRglc as well as clinical and electrophysiological examinations were normal in all cases at the beginning of the study. Four of the mutation carriers developed typical FFI during the study but CMRglc and the clinical and electrophysiological examinations remained normal 63, 56, 32 and 21 months, respectively before disease onset. The carrier whose tests were normal 32 months before disease onset was re-examined 13 months before the onset. At that time, selective hypometabolism was detected in the thalamus while spectral-EEG analysis disclosed an impaired thalamic sleep spindle formation. Following clinical disease onset, CRMglc was reduced in the thalamus in all 3 patients examined. Our data indicate that the neurodegenerative process associated with FFI begins in the thalamus between 13 and 21 months before the clinical presentation of the disease.
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PMID:Pre-symptomatic diagnosis in fatal familial insomnia: serial neurophysiological and 18FDG-PET studies. 1639 7

Fibromyalgia is a prevalent syndrome characterized by chronic pain, fatigue, and insomnia. Patients with fibromyalgia commonly have an elevated body mass index and are physically inactive, 2 major risk factors for metabolic syndrome. Yet little is known about the relationship between chronic pain conditions and metabolic disturbances. Our study evaluated the risk for, and neuroendocrine correlates of, metabolic syndrome in this patient population. Women with fibromyalgia (n = 109) were compared with control healthy women (n = 46), all recruited from the community. Metabolic syndrome was identified by using criteria from the Adult Treatment Panel III with glycosylated hemoglobin concentrations substituted for serum glucose. Catecholamine and cortisol levels were determined from 12-hour overnight urine collections. Women with fibromyalgia were 5.56 times more likely than healthy controls to have metabolic syndrome (95% confidence interval, 1.25-24.74). Fibromyalgia was associated with larger waist circumference (P = .04), higher glycosylated hemoglobin (P = .01) and serum triglyceride (P < .001) levels, and higher systolic (P = .003) and diastolic (P = .002) blood pressure. Total and low-density lipoprotein cholesterol were also significantly higher in women with fibromyalgia (P = .001 and .02, respectively), although high-density lipoprotein cholesterol was in the reference range. These associations were not accounted for by age or body mass index. Meeting criteria for more metabolic syndrome components was related to higher urinary norepinephrine (NE)/epinephrine and NE/cortisol ratios (P < .001 and P = .009, respectively). Women with chronic pain from fibromyalgia are at an increased risk for metabolic syndrome, which may be associated with relatively elevated NE levels in conjunction with relatively reduced epinephrine and cortisol secretion.
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PMID:Metabolic syndrome in women with chronic pain. 1716 Dec 30

A 70-year-old man developed herpes zoster over the right L5-S2 region for 3 days and was admitted for acyclovir therapy. He had a medical history of rectal cancer status post-colostomy and end-stage renal disease undergoing thrice weekly hemodialysis. Without a prior loading dose, acyclovir 500 mg (7.7 mg/kg) daily was given intravenously in two divided doses. On the third dosage, the patient became confused and agitated and developed insomnia. Within the following 24 h, delirium, visual and auditory hallucinations, disorientation to place and time, as well as impaired recent memory occurred. At the same time, a transient low grade fever (38 degrees C) was noted but resolved spontaneously after ice pillow (Fig. 1). The etiology was vigorously explored. He had no history of any neurological or psychiatric disorders. Drug history was reviewed, but no other medications besides acyclovir were currently being used. Physical examination revealed neither meningeal signs nor focal neurological deficits. Serum blood urea nitrogen, glucose, and electrolytes were within normal limits except for an elevated creatinine level at 6.2 and 5.7 mg/dl (before and after neuropsychotic symptoms, respectively). Complete blood count with differentiation was also unremarkable. Cerebrospinal fluid examination was not possible as the patient's family refused the lumbar puncture. Moreover, an electroencephalograph study and head computed tomography scan disclosed no abnormalities. Acyclovir-induced neurotoxicity was suspected. Therefore, acyclovir was discontinued. Subsequently, serum acyclovir and CMMG were checked by enzyme-linked immunosorbent assay. Serum acyclovir level was 1.6 mg/l (normal therapeutic level, 0.12-10.8 mg/l) and CMMG level was 5 mg/l. Emergent hemodialysis (4-h/session) was given; the neuropsychotic symptoms, including agitation, delirium, and visual and auditory hallucinations, greatly abated after the second session. The patient fully recovered after three consecutive days of hemodialysis; the serum was rechecked and revealed that the acyclovir level was below 0.5 mg/l and the CMMG level was undetectable. At the same time, his herpetic skin lesions resolved well.
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PMID:Acyclovir-induced neuropsychosis successfully recovered after immediate hemodialysis in an end-stage renal disease patient. 1765 Nov 80

Iloperidone, a mixed D2/5-HT2 antagonist, is currently in clinical development for the treatment of schizophrenia. This article assesses the short-term safety of iloperidone using a pooled analysis of 3 phase 2, short-term acute schizophrenia studies conducted between 1998 and 2002 (N = 1943). Patients exposed to 3 dose ranges of iloperidone, another antipsychotic, or placebo were compared on rates of serious adverse events (SAEs), adverse events (AEs), extrapyramidal symptoms, akathisia, prolactin, weight and metabolic parameters, QTc, and other standard safety parameters. The most common treatment-related AEs observed with iloperidone were dizziness, headache, dry mouth, nausea, and insomnia. Discontinuation due to AEs was 4.8% for iloperidone, 7.6% for haloperidol, 6.2% for risperidone, and 4.8% for placebo. Iloperidone groups showed better overall performance on the Extrapyramidal Symptom Rating Scale and Barnes Akathisia Scale than risperidone or haloperidol groups. Patients taking iloperidone experienced a mild weight increase (range, 1.5-2.1 kg) similar to that of risperidone (1.5 kg), whereas those on haloperidol and placebo showed mean weight loss (-0.1 kg and -0.3 kg, respectively). QTc interval significantly increased across all iloperidone groups (least squares mean change from baseline to end point, 2.9-9.1 msec) and for haloperidol (5.0 msec). No significant QTc changes occurred in the risperidone or placebo groups. Iloperidone was associated with no change from baseline in total cholesterol, mild elevation in serum glucose, and slight decrease in triglycerides. Prolactin levels decreased with iloperidone and increased significantly with risperidone and haloperidol. These short-term trials suggest that iloperidone has a reassuring safety profile in many of the areas that are of potential concern, including relatively low dropout rates because of AEs, low extrapyramidal symptoms, akathisia, and prolactin elevation, and a modest short-term effect on weight gain.
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PMID:Safety profile of iloperidone: a pooled analysis of 6-week acute-phase pivotal trials. 1833 8

The purpose of the work was assessment of clinical efficiency of OT and study of cerebral blood flow indices in combined treatment of DEP patients, including OT. It was detected that addition of intravenous OT in a complex of planned therapy of DEP patients at the age about 60 years leaded to more significant and more rapid (vs. control groups) regress of DEP symptoms, in the first place headache, ear noise, sleeplessness, memory reduce. Decrease in objective manifestation of neurological syndromes such as dysmnesic, akineticorigid, asthenic ones. Blood lipid spectrum, blood glucose level, blood coagulant system and cerebral blood flow indices were improved. These effects were more expressive in patients with the age less than 60 years. In control subgroups these changes were less expressed. Thus, of OT in combined treatment of patients with DEP improved efficiency of drug therapy and accelerated regress of various symptoms of this pathology, especially in patients with the age less than 60 years.
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PMID:[Use of ozonotherapy (OT) in combined treatment of patients with discirculatory encephalopathy (DEP)]. 1850 80

In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11.
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PMID:BT-11 improves stress-induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains. 1871 49


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