Alcohol-induced cognitive disorder is a very severe problem in problem alcohol drinker and alcohol itself seems to be one of the main causalities in the development of senile dementia. However, the spectrum of alcohol induced cognitive disorder is quite broad, for example, it covered from alcohol-induced persistent amnestic disorder to Wernicke-Korsakoff syndrome and alcohol-induced persistent dementia. By that reason, broad spectrum of cognitive impairment by excessive alcohol drinking is regarded as alcohol related dementia. The pharmacological treatment is not well established yet in alcohol related dementia, except Wernicke-Korsakoff syndrome which is definitely related to thiamine deficiency. Therefore we introduced that some reports about the clinical efficacies by rivastigmine or donepezil trial and recent outcomes of memantine trial by authors in this review.
Alcohol Drinking ; Alzheimer Disease ; Dementia ; Indans ; Korsakoff Syndrome ; Memantine ; Phenylcarbamates ; Piperidines ; Rivastigmine ; Thiamine ; Thiamine Deficiency

OBJECTIVES: Despite the fact that delirium is a frequent neuropsychiatric disorder in cancer patients, there are, in Korea, no guidelines for the pharmacological treatment of such delirium. This systematic review evaluated the efficacy and safety of some pharmacological interventions and summarized the results. METHODS: We searched PubMed, Embase, CINAHL, the Cochrane Library, and the KMbase, targeting from January 1990 to October 2008, using key words. Moreover, we included systematic reviews, meta-analyses, and randomized controlled trial literature in the search. Then, we stratified the trials based on their evidence levels. RESULTS AND CONCLUSION: We identified 13 randomized, controlled studies and 2 case-control studies that met our inclusion criteria. These showed that haloperidol was the medication of choice to treat delirium. In addition, they revealed that atypical antipsychotics have not shown clear superiority with regard to effectiveness as compared to haloperidol. Neither donepezil nor rivastigmine were shown to be effective in preventing or treating delirium.
Antipsychotic Agents ; Case-Control Studies ; Delirium ; Haloperidol ; Humans ; Indans ; Korea ; Phenylcarbamates ; Piperidines ; Rivastigmine

OBJECTIVETo optimize the synthetic procedure of S-(+)-rivastigmine hydrogentartrate which was known as an agent for the treatment of Alzheimer disease.

METHODSS-(+)-rivastigmine hydrogentartrate was synthesized by using 1-(3-hydroxyphenyl)ethanone as the starting material via oximation, reduction and N-methylation to produce the key intermediate 3-1-dimethylaminoethylphenol, which finally reacted with N-ethyl-N-methylcarbamoyl chloride. The enantiomers were resolved with di-(+)-p-toluoyl-D-tartaric acid, and the title compound was prepared by mixing S-rivastigmine base with L-(+)-tartrate.

RESULTSThe total yield of S-(+)-rivastigmine hydrogentartrate was 4.17%.

CONCLUSIONThe materials in this procedure are all commercially available. The reaction conditions are mild and total yield is high.

Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Models, Chemical ; Molecular Structure ; Phenylcarbamates ; chemical synthesis ; chemistry ; Rivastigmine ; Stereoisomerism

Despite epidemiological studies reporting no negative effects of mild to moderate alcohol drinking on cognitive functioning, a recent well-controlled study showed that chronic mild drinking diminished the volume of the brain and was associated with cognitive decline that worsened as a function of the amount of alcohol consumed. Animal studies have demonstrated that neural cell damage follows chronic alcohol intake and withdrawal. In addition, acute excessive alcohol intake has been shown to result in temporary impairment of memory, and chronic alcohol drinking is often related to neuronal damage and cognitive disorders. Even though a diverse spectrum of cognitive disorders can develop after sustained alcohol drinking, no definite diagnostic criteria existed before those proposed by Oslin; the availability of these criteria will provide more structured clinical and academic approaches to alcohol-related cognitive decline, including dementia. In general, diminished cognitive functioning has been related to excessive alcohol consumption, with cognitive functioning gradually recovering over time. With the exception of the administration of thiamine in Wernicke-Korsakoff syndrome, only supportive pharmacotherapies have been provided for patients with alcohol-related cognitive disorders. However, experimental trials with rivastigmine or donepezil have been conducted for special populations with persistent cognitive impairments, and these studies reported favorable outcomes. We administered memantine for alcohol-related dementia and observed improvements in verbal memory and scores on the mini-mental status exam. We anticipate that novel and appropriate therapeutic agents for various conditions in this domain will be developed based on systematic diagnostic criteria and the accumulation of neurobiological evidence about alcohol-related cognitive decline.
Alcohol Drinking ; Alcoholism ; Animals ; Brain ; Dementia ; Drinking ; Humans ; Indans ; Korsakoff Syndrome ; Memantine ; Memory ; Neurons ; Phenylcarbamates ; Piperidines ; Thiamine ; Rivastigmine

The target compounds were prepared from 5-aminobenzimidazolone by two steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The AChE inhibitory activity of compound 4d is the best of them, and its IC50 value is equal to 7.2 μmol·L(-1), which is better than that of rivastigmine; moreover the 4d had no inhibitory activities to BuChE. Therefore, the inhibitory activities of 5-aminobenzimidazolone derivatives to acetylcholinesterase are worth further researching.
Acetylcholinesterase ; metabolism ; Benzimidazoles ; chemical synthesis ; chemistry ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Phenylcarbamates ; chemistry ; Rivastigmine ; Structure-Activity Relationship

BACKGROUND AND PURPOSE: The goal of this study was to estimate the efficacy and safety of the rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD) who cannot tolerate or do not respond to oral cholinesterase inhibitors (ChEIs). METHODS: A 24-week, prospective, open-label, single-arm, multicenter study was conducted from June 2009 to June 2010 in patients with probable AD. The enrolled patients had either a poor response or a decline in global function after treatment with oral ChEIs, or they were not able to tolerate treatment with oral ChEIs due to adverse events such as nausea or vomiting. A poor response was defined as a decrease of at least 2 points on the Korean version of the Mini-Mental State Examination (K-MMSE) within the previous 6 months (the decline in global function was determined by the investigator or caregiver). The efficacy of treatment was assessed using a follow-up Clinical Global Impression of Change (CGIC) assessment and K-MMSE conducted after 24 weeks, and safety was measured by the occurrence of adverse events and patient disposition. RESULTS: In total, 164 patients aged 74.7+/-7.52 years (mean+/-SD) and with 5.12+/-3.64 years of education were included. The study was completed by 70% of the patients (n=116), with 12.2% discontinuing due to adverse events. The most frequently reported adverse events (11%) were skin lesions, such as erythema or itching, followed by gastrointestinal problems (1.2%). Either an improvement or no decline in CGIC scores was reported for 82% of the patients. CONCLUSIONS: The immediate switching of patients from an oral ChEI to the rivastigmine transdermal patch without a washout period was safe and well tolerated by the probable-AD patients in this study.
Aged ; Alzheimer Disease ; Cholinesterase Inhibitors ; Cholinesterases ; Erythema ; Follow-Up Studies ; Humans ; Nausea ; Phenylcarbamates ; Prospective Studies ; Pruritus ; Research Personnel ; Skin ; Transdermal Patch ; Vomiting ; Rivastigmine

Although acetylcholinesterase inhibitors (e.g., tacrine, donepezil, rivastigmine, and galantamine) and NMDA receptor antagonists (e.g., memantin) have demonstrated efficacy in the temporal symptomatic control of cognitive decline and daily function in Alzheimer's disease (AD) patients, their effect is not good enough to restore premorbid function, nor is it maintained in the later stages. Therefore, nonpharmacological interventions are being increasingly advocated in order to optimize the cognition, affect and global functioning of AD patients. We reviewed the current nonpharmacological interventions for AD. Nonpharmacological interventions can be divided into two groups. One is cognitive interventions (e.g., Memory rehabilitations, Reality orientation, Reminiscence therapy and so on) and the other is behavioral interventions (e.g., unmet needs interventions, learning and behavioral interventions, environmental vulnerability and reduced stress-threshold interventions). Cognitive interventions are aimed to slow and compensate cognitive decline of AD patients. On the other hand, behavioral interventions are aimed to reduce neuropsychiatric symptoms (depression, anxiety, agitation, wandering, aggression and so on) of AD patients. Although many of the nonpharmacological interventions have proven beneficial for AD patients, their efficacy was still ambiguous. Randomized and controlled study with a larger sample size is needed to confirm efficacy of nonpharmacological interventions.
Aggression ; Alzheimer Disease ; Anxiety ; Cholinesterase Inhibitors ; Cognition ; Dihydroergotamine ; Hand ; Humans ; Indans ; Learning ; Memory ; N-Methylaspartate ; Orientation ; Phenylcarbamates ; Piperidines ; Rivastigmine ; Sample Size ; Tacrine

To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.
Administration, Intranasal ; Animals ; Area Under Curve ; Chromatography, Liquid ; Drug Carriers ; Drug Compounding ; Liposomes ; Male ; Neuroprotective Agents ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Particle Size ; Phenylcarbamates ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Rivastigmine ; Tandem Mass Spectrometry

Many new antiepileptic drugs (AEDs) have been developed in the last two decades, contributing to the optimal treatment for childhood epilepsy. The goal of the treatment is to achieve seizure-free without any side effects, that deteriorates the quality of life by causing negative consequences. The new AEDs have not shown better efficacy, but generally seem to be better tolerated, having fewer systemic reactions and better pharmacokinetics than the established AEDs. The new AEDs have a broad spectrum of activities, which offer new opportunities to patients who have not shown any favorable responses to the established ones. There are more choices when trying to select AEDs for epileptic seizures and syndromes. Majority of the new AEDs have more than one action mechanism. AEDs acting selectively through the GABAergic system are tiagabine and vigabatrin; acting by inhibition of voltagedependent Na+ and Ca2+ channels are lamotirigine, oxcabarbazepine and topiramate; and acting by inhibition of glutamate-mediated excitation are felbamate, topiramate. The pharmacokinetic parameters of the new AEDs compared to the established AEDs, new AEDs have improved in terms of longer half-lives, permitting less frequent daily dosing, reduced potential for drug interactions. Considerations in selecting an AEDs are not only dependent on seizure types or syndromes, side effect profile, action mechanism, drug interaction, pharmacokinetic profile, facility of drug initiation, but also on age and sex of patients. Patients with worsened seizurefrequency or development of new types of seizure after the introduction of AEDs, should be questioned on the previously diagnosed seizure types or syndromes.
Anticonvulsants ; Drug Interactions ; Epilepsy ; Fructose ; Humans ; Nipecotic Acids ; Phenylcarbamates ; Propylene Glycols ; Quality of Life ; Seizures

This paper specifically discusses the risk assessment on the pesticide residues in vegetables collected from traditional markets, big marts and departments in the southern part of Seoul. Vegetable samples were 6,583 cases from January to December in 2009. Monte-Carlo simulation was used to calculate the uncertainty for the risk index using pesticide residues, average dietary intake for vegetables and acceptable daily intake. Deterministic risk indexes were 7.33% of diethofencarb, 5.13% of indoxacarb, 3.96% of EPN, 3.92% of diniconazole and 3.09% of chlorothalonil, respectively. And other pesticides were below 3%. Distributions of risk indexes obtained by the Monte-Carlo simulations were similar to the deterministic values, even though the confidence intervals for 95% were very wide. We confirmed that health risks caused by eating vegetables exceeded maximum residue limits of pesticide are very low and the population is generally safe, judging from the risk indexes located between 0.07 to 9.49%.
Eating ; Korea ; Nitriles ; Oxazines ; Pesticide Residues ; Pesticides ; Phenylcarbamates ; Risk Assessment ; Triazoles ; Uncertainty ; Vegetables