Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. In addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions.
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PMID:Donepezil: a clinical review of current and emerging indications. 1468 Apr 45

Acetyl Cholinesterase (AChE) inhibitors such as Donepezil, Rivastigmine and Galantamine are approved by US-FDA as first line drugs to treat the cognitive symptoms of Alzheimer's disease (AD). Their beneficial effects are attributed to their ability to elevate endogenous acetylcholine (ACh) at the M1 muscarinic receptor in the brain. However, their side effects such as nausea, vomiting, dizziness, insomnia, loss of appetite and altered heart rate are related to non-specific activation of M2-M5 muscarinic subtypes in various tissues. It is logical, therefore, to develop agonists with M1 receptor selectivity. Unfortunately, this is limited due to a high degree of orthosteric site homology among the receptor subtypes. In contrast, their allosteric sites are unique and, therefore, allow selective targeting using positive allosteric modulators (PAMs). PAMs of M1 receptors are devoid of agonist activity, however, when bound they enhance the binding affinity of orthosteric ligand, ACh. The major limitation of these PAMs is their bioavailability in the brain. In the current hypothesis, we propose surface modified nano-lipid drug conjugates (LDC-NPs) of PAMs of M1 receptors to improve their bioavailability in brain. When co-administered with AChE inhibitors they are expected to increase their efficacy and reduce their therapeutic dose and side effects.
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PMID:Surface modified nano-lipid drug conjugates of positive allosteric modulators of M1 muscarinic acetylcholine receptor for the treatment of Alzheimer's disease. 2835 83

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including causing abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that chronic waterborne exposure to DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.
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PMID:Evaluation of the Adverse Effects of Chronic Exposure to Donepezil (An Acetylcholinesterase Inhibitor) in Adult Zebrafish by Behavioral and Biochemical Assessments. 3296 60

Donepezil is a cholinesterase inhibitor used extensively to treat Alzheimer's disease. The increased cholinergic activity is associated with adverse effects, therefore gastrointestinal symptoms, including nausea, vomiting, and diarrhea, are common. Hypokalemia is a rare adverse event that occurs in less than 1% of donepezil-treated patients. Although hypokalemia of mild and moderate grade does not present serious signs and symptoms, severe hypokalemia often results in prolonged hospitalization and mortality. Herein, we report a case of hypokalemia developed after the initiation of donepezil therapy for cognitive impairment.
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PMID:Development of donepezil-induced hypokalemia following treatment of cognitive impairment. 3304 4


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