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Am J Alzheimers Dis Other Demen. 2008 Jun-Jul; 23(3): 286-90
Modrego PJ, Monleon I, Sarasa M
To date there are no conclusive reports on the usefulness of determining amyloid peptides in the serum of patients with Alzheimer's disease (AD). Only anecdotal works deal with the changes in the peptides produced by cholinesterase inhibitors. In this study, the authors investigated and studied the clinical significance of plasmatic Abeta-40 and Abeta-42 peptide levels in a series of 34 consecutive patients with AD. The baseline levels of the Abeta-40 peptide correlated negatively with the Mini Examen Cognoscitivo (Spanish version of the Mini-Mental test) score. Complete follow-up was possible in 22 patients. After 6 months of treatment with galantamine, the mean Abeta-40 peptide levels decreased from 31.86 to 24.22 pg/mL. The baseline levels of Abeta-40 were predictive of response to treatment in the Alzheimer's Disease Assessment Scale-Cognitive Subscale. The authors conclude that determining plasmatic Abeta-40 peptide levels could be useful in predicting and monitoring response to treatment in AD.
Study of neuroprotection of donepezil, a therapy for Alzheimer's disease.
Chem Biol Interact. 2008 May 7;
Akasofu S, Kimura M, Kosasa T, Sawada K, Ogura H
Donepezil is a potent acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease. Although acetylcholinesterase inhibitors are thought to be symptomatic treatment of Alzheimer's disease, it is not clear whether they are effective against progressive degeneration of neuronal cells. In this study, we investigated the neuroprotective effects of donepezil against ischemic damage, N-methyl-d-aspartate (NMDA) excitotoxicity, and amyloid-beta (Abeta) toxicity using rat brain primary cultured neurons. Lactate dehydrogenase (LDH) released into the culture medium was measured as a marker of neuronal cell damage. As an ischemic damage model, we used oxygen-glucose deprivation in rat cerebral cortex primary cultured neurons. Pretreatment with donepezil (0.1, 1 and 10muM) significantly decreased LDH release in a concentration-dependent manner. However, other acetylcholinesterase inhibitors (galantamine, tacrine and rivastigmine) did not significantly decrease LDH release. In a NMDA excitotoxicity model, pretreatment with donepezil (0.1, 1 and 10muM) decreased the LDH release in a concentration-dependent manner. In binding assay for glutamate receptors, donepezil at 100muM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. We further examined the effect of donepezil on Abeta (1-40)- and Abeta (1-42)-induced toxicity in primary cultures of rat septal neurons. Pretreatment with donepezil (0.1, 1 and 10muM) significantly decreased LDH release induced by Abetas in a concentration-dependent manner. However, other acetylcholinesterase inhibitors (galantamine and tacrine) and NMDA receptor antagonists (memantine and dizocilpine (MK801)) did not significantly decrease LDH release. These results demonstrate that donepezil has protective effects against ischemic damage, glutamate excitotoxicity and Abeta toxicity to rat primary cultured neurons and these effects are not dependent on acetylcholinesterase inhibition and antagonism of NMDA receptors. Thus, donepezil is expected to have a protective effect against progressive degeneration of brain neuronal cells in ischemic cerebrovascular disease and Alzheimer's disease.
Effects of galantamine on cognitive deficits in smokers and non-smokers with schizophrenia.
Schizophr Res. 2008 Jun 18;
Sacco KA, Creeden C, Reutenauer EL, George TP
The safety and tolerability of galantamine in patients with epilepsy and memory difficulties.
Epilepsy Behav. 2008 Aug; 13(2): 376-80
Griffith HR, Martin R, Andrews S, LeBron Paige A, Ware J, Faught E, Welty T
Individuals with epilepsy commonly experience memory loss. We investigated the safety and tolerability of galantamine in treatment of memory loss in a pilot study of 28 patients with epilepsy, randomly assigned to galantamine (n=13) or placebo (n=15) and followed for a total of 12 weeks. Participants underwent blinded memory assessment at baseline and 12 weeks (Selective Reminding Test, 7/24 Spatial Recall). One participant in the galantamine group had a suspected recurrence of brain neoplasm and increased seizures; all other participants receiving galantamine showed no increase in seizure activity during the trial. Patients in both groups reported mild, tolerable side effects (headache, appetite suppression), with no difference between groups. No significant differences were observed on the memory measures when both groups were retested at Week 12. Galantamine appears to be safe and tolerable in patients with epilepsy. Further studies with larger samples and comparison with other cholinesterase inhibitors should be considered.
Schizophr Res. 2008 Jun 10;
Kelly DL, McMahon RP, Weiner E, Boggs DL, Dickinson D, Conley RR, Buchanan RW
Cigarette smoking is in schizophrenia is prevalent and may be due to self-medicating attempts to improve cognitive deficits related to alpha7 and alpha4beta2 nicotinic receptor dysregulation. Galantamine is an acetylcholinesterase inhibitor that acts as a positive allosteric modulator of nicotine acetylcholine receptors including both the alpha4beta2 and alpha7 subunits. In a double-blind randomized clinical trial galantamine was compared to placebo for its effects on cognitive functioning in people with schizophrenia. This manuscript reports findings for galantamine's effect on smoking behavior in people from this 12-week trial who were smokers (18 galantamine, 25 placebo). Expired CO was measured every 2 weeks and the Fagerström Test for Nicotine Dependence (FTND) was administered at baseline and endpoint. Expired CO measures in galantamine subjects were 23.0+/-9.7 ppm and 21.1+/-10.3 ppm at baseline and Week 12, respectively, compared to 20.1+/-8.5 ppm and 21.0+/-10.3 ppm at baseline and Week 12 in placebo subjects. The mean tau-b correlation between expired CO level and visit was -0.05+/-0.41 in the galantamine group and 0.13+/-0.42 in the placebo group (F =0.73, df=1,38, p=0.40), suggesting that there were no trends toward increased or decreased smoking in either group. Mean FTND scores in the galantamine group were 4.9+/-2.5 at baseline and 5.2+/-2.2 at Week 12, compared to 4.1+/-2.6 at baseline and 3.7+/-2.6 at Week 12 in the placebo group (Mantel-Haenszel chi(2)=5.53, df=1, p=0.019), for an effect size of 0.4. These results suggest that galantamine has no effect on cigarette smoking and that during galantamine treatment nicotine dependency scores worsen.
Clin Drug Investig. 2008; 28(7): 429-37
Gil P, Ayuso JL, Marey JM, Antón M, Quilo CG
BACKGROUND AND OBJECTIVES: There is frequently a degree of variability among different types of dementia specialists in clinical practice in both the clinical diagnosis and the management of patients with Alzheimer's disease and cerebrovascular disease (CVD). This variability may have an adverse effect on the use of medical resources as well as on patients' well-being. The main objective of this study was to describe the current diagnosis and management of patients with Alzheimer's disease and CVD in Spain. Other objectives were to determine whether there were significant differences in the diagnosis and management of these patients depending on physician characteristics and/or patient profile. METHODS: This was an epidemiological, cross-sectional, multicentre study in which 107 physicians participated and recruited patients with Alzheimer's disease and CVD. During a 1-month period, physicians collected data on diagnosis, treatment, follow-up, adverse events and other characteristics of these patients. This study was performed under naturalistic conditions, and no restrictions were imposed on the physicians. RESULTS: Physicians were mainly neurologists (76%), geriatricians (14%) and psychiatrists (8%) with a median age of 42 years. A total of 720 patients with a diagnosis of Alzheimer's disease and CVD were recruited. The median age of the patients was 78 years. Almost all patients were diagnosed by neuroimaging (98%) together with medical history (87%). The existence of a previous stroke coincident with cognitive deterioration was used as a diagnostic method in only 27% of patients. Among non-pharmacological treatment measures, diet was the most frequently recommended (61%), followed by cognitive stimulation (50%) and physical exercise (44%). The most commonly used pharmacological treatments were galantamine (59%), donepezil (14%) and rivastigmine (11%). The incidence of adverse events was low (3%), and all were considered non-severe. There were no significant correlations between physician age or physician years of practice and the diagnostic method used. The diagnostic method most frequently used by psychiatrists (100%) and geriatricians (97%) was medical history whereas this method was not used as much by neurologists (85%) [p = 0.0150]. Neuroimaging methods were more frequently used by neurologists (99%) and geriatricians (96%) compared with psychiatrists (84%) [p < 0.0001]. Patients with attention disorders had a higher frequency of follow-up visits (p = 0.0145) and were treated less frequently with donepezil (p = 0.0118). CONCLUSIONS: Several possible areas of improvement in the management of patients with Alzheimer's disease and CVD were identified. These included better control of cardiovascular risk factors, such as hypertension and hyperlipidaemia, which have a high prevalence in this population, as has been shown in the present study. These potentially modifiable risk factors may assist in the prevention of Alzheimer's disease. Also identified was the need to emphasize the role of general practitioners in decreasing the time to diagnosis of Alzheimer's disease. Development of well designed clinical practice guidelines may help physicians decide on the most appropriate ways of diagnosing and managing patients with Alzheimer's disease and CVD and reduce practice variations between different medical specialities.
Analyses of mortality risk in patients with dementia treated with galantamine.
Acta Neurol Scand. 2008 Jun 1;
Feldman HH, Pirttila T, Dartigues JF, Everitt B, Van Baelen B, Brashear HR, Berlin JA, Battisti WP, Kavanagh S
Objective - To analyze mortality data from patients with Alzheimer's disease (AD), Alzheimer's plus cerebrovascular disease (AD + CVD) or vascular dementia (VaD). Methods - (1) Meta-analysis of mortality data from double-blind, placebo-controlled, randomized trials; and (2) recontact study to collect additional longer term mortality data from previous galantamine trial participants. Results (meta-analysis) - Across 12 trials ( vs
Prevalence of cholinesterase inhibitors in subjects with dementia in Europe.
Pharmacoepidemiol Drug Saf. 2008 May 29;
Pariente A, Helmer C, Merliere Y, Moore N, Fourrier-Réglat A, Dartigues JF
PURPOSE: To evaluate the prevalence of cholinesterase inhibitor (ChI) treatment in subjects with dementia in European countries. METHODS: We studied the prevalence of treatment in subjects with dementia among European countries in 2004 (Belgium, France, Germany, Italy, the Netherlands, Poland, Portugal, Spain and the United Kingdom) by using estimates of prevalence of dementia and of ChI treatments according to sales and reimbursement data. RESULTS: In 2004, estimated prevalence of ChI use among subjects with dementia ranged from 3.0% in the Netherlands to 20.3% in France. It was 17.5% in Spain, 6.7% in the UK and 5.9% in Italy. Donepezil was used by more than 60% of patients using a single ChI and represented almost 50% of reimbursements for patients that had used at least two different ChIs during the year. Galantamine and rivastigmine were respectively used by 22 and 18% of subjects using a single drug and 27 and 23% of reimbursements for patients that had used at least two different ChIs. Nevertheless, different patterns of use were found for individual countries. CONCLUSIONS: Prevalence of treatment by ChIs among subjects with dementia remains weak and varies greatly across Europe. Differences in reimbursement rates and health policies could partly explain these variations, as ChIs could have failed to convince health authorities because the outcomes considered for trials are not used by clinicians in their everyday practice. If donepezil was highly predominant across countries, variations in rivastigmine and galantamine importance could reflect local market specificities. Copyright (c) 2008 John Wiley & Sons, Ltd.
Galantamine-induced pisa syndrome: memantine as an alternative.
Int J Geriatr Psychiatry. 2008 Jun; 23(6): 660-1
Chen CF, Hsu HC, Ouyang WC, Lin YC
AAFP and ACP release guideline on dementia treatment.
Am Fam Physician. 2008 Apr 15; 77(8): 1173-5
Graham L