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Cholinesterase Inhibitors (cholinesterase + inhibitor)
Kinds of Cholinesterase Inhibitors Selected AbstractsADHERENCE TO CHOLINESTERASE INHIBITORS IN PATIENTS WITH ALZHEIMER'S DISEASEJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2009Lucie Blais PhD No abstract is available for this article. [source] A Post-ischaemic Single Administration of Galanthamine, a Cholinesterase Inhibitor, Improves Learning Ability in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2000A. I. ILIEV Transient forebrain ischaemia is widely observed in clinical practice. We have examined the effect of a single administration of the Cholinesterase inhibitor galanthamine (2 mgkg,1, i.p.) 25 min after reperfusion in male Sprague-Dawley rats (180 ± 20 g) after a 20-min common carotid artery occlusion. Twenty-four-hours post-ischaemia there was no difference in motor co-ordination or muscle tonus of the rats treated with or without galanthamine as assessed by the rota-rod test. Learning ability was examined using the shuttle-box test, evaluating the latency time and the number of errors for six days in succession. The performance of the ischaemic saline-injected rats was significantly impaired on days 4, 5, 6 (latency time) compared with the non-ischaemic rats and with the ischaemic animals administered galanthamine (P< 0.05). Similar results were obtained when counting the number of errors (failure to cross the cage during conditioned or unconditioned stimulus). The monitoring of body temperature during the first 12-h post-ischaemia did not show any significant difference between the groups. The data showed a beneficial effect of galanthamine on the recovery of learning ability when administered once only post-ischaemia. This suggests a direct effect on the early pathologic mechanisms of CNS damage. Cholinesterase inhibitors may prove useful in the early clinical treatment of ischaemic conditions. [source] Clinical predictors of response to acetyl cholinesterase inhibitors: experience from routine clinical use in NewcastleINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 10 2003S. Pakrasi Abstract Background Acetyl Cholinesterase Inhibitors (AChEIs) have been in clinical use for the past five years in the UK for the symptomatic treatment of Alzheimer's disease (AD). There are few data on the patterns and predictors of response to AChEI therapy in routine clinical practice. We therefore investigated clinical variables that may distinguish between AChEI responders and non-responders. Methods A retrospective sample of 160 consecutive patients with dementia who were treated on clinical grounds with an AChEI was studied. Treatment response was defined in two ways: (a) A clinical response was achieved when there was no deterioration or there was an improvement on a global clinical assessment (CGI) and (b) a Mini-Mental-State-Examination (MMSE) response when there was an improvement of 2 or more MMSE points. Results A total of 62 (45%) patients achieved an MMSE response. A diagnosis of dementia with Lewy Bodies (DLB) and Parkinson's disease+Dementia (PDD) was associated with a MMSE response, as were hallucinations, and lower MMSE scores at baseline. 125 (78%) patients achieved a CGI response for which there were no clinical predictors. Conclusions Severity of illness, a diagnosis of DLB and PDD, and presence of hallucinations at baseline were predictive of a MMSE response. Non-AD dementia and severe dementia responded equally well to AChEI treatment and results of further randomised, placebo-controlled studies are needed to clarify the role of AChEI in the treatment of these disorders. Copyright © 2003 John Wiley & Sons, Ltd. [source] Changes in utilisation of anticholinergic drugs after initiation of cholinesterase inhibitors,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2009M Robinson BPharm, MedSc Abstract Purpose Cholinesterase Inhibitors (CEIs) have been subsidised in Australia since February 2001 for cognitive decline associated with mild to moderate Alzheimer disease. The number of people with Alzheimer Disease is expected to increase, with a continuing increase in the number of people receiving CEI's. Many anticholinergic drugs (ACDs) are also prescribed to people receiving CEIs and concerns about the impact of the interaction have been raised. The aim of this study was to describe co-prescribing of a group of important ACDs in patients initiating treatment with CEIs in Australia. Methods Pharmacy claim data for Australia (Pharmaceutical Benefits Scheme) was examined for the period 1 April to 30 June 2006. All selected prescriptions supplied for patients receiving their first supply of any CEIs (initiators) were extracted for 14 weeks prior to and post the first date of supply. The numbers of initiating people co-administering CEIs and ACDs was examined. Results 5797 persons received their first prescription for CEIs between 1 April and 30 June 2006. Thirty-two per cent of these also received prescriptions for at least one ACD. There was a statistically significant increase in the number of initiators receiving an ACD. The significant increase was in patients receiving atypical antipsychotics. There was a trend towards an increase in patients receiving oxybutynin. Conclusions Extent of co-administration of ACDs and CEIs is similar to other international studies however the most significant increase is seen in patients receiving atypical antipsychotics. The implications of adding atypical antipsychotics are potential for worsening disease, increasing adverse effects and increased health resource utilisation in this vulnerable group. Copyright © 2009 John Wiley & Sons, Ltd. [source] A review of studies describing the use of acetyl cholinesterase inhibitors in Parkinson's disease dementiaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2005I. D. Maidment Objective:, To review the literature relating to the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia (PDD). Method:, MEDLINE (1966 , December 2004), PsychINFO (1972 , December 2004), EMBASE (1980 , December 2004), CINHAL (1982 , December 2004), and the Cochrane Collaboration were searched in December 2004. Results:, Three controlled trials and seven open studies were identified. Efficacy was assessed in three key domains: cognitive, neuropsychiatric and parkinsonian symptoms. Conclusion:, Cholinesterase inhibitors have a moderate effect against cognitive symptoms. There is no clear evidence of a noticeable clinical effect against neuropsychiatric symptoms. Tolerability including exacerbation of motor symptoms , in particular tremor , may limit the utility of cholinesterase inhibitors. [source] Treatment of behavioural symptoms and dementia in Parkinson's diseaseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2005Hasmet A. Hanagasi Abstract Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD. [source] Cholinesterase inhibitors in Alzheimer's diseaseHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2001Roger Bullock No abstract is available for this article. [source] Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer's disease: a reviewINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2009A. Kurz Summary Background:, Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer's disease (AD) (including the USA, Latin America, Europe and Asia). Objectives:, To review the available pharmacokinetic data that supported the rationale behind the development of the rivastigmine transdermal patch and its clinical effects in dementia therapy. This article will also discuss how the patch may alter the treatment paradigm for patients with AD. Results:, The 9.5 mg/24 h rivastigmine patch was shown to provide comparable exposure to the highest recommended doses of capsules (12 mg/day) with significantly lower maximum plasma concentration (Cmax 8.7 vs. 21.6 ng/ml) and slower absorption rate (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated into similar efficacy with three times fewer reports of nausea and vomiting (7.2% vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the 9.5 mg/24 h patch group achieved their target therapeutic dose at the end of the study, compared with those in the 12 mg/day capsule group (95.9% vs. 64.4%). Conclusion:, The rivastigmine patch provides continuous drug delivery over 24 h and similar efficacy to the highest recommended dose of oral rivastigmine with improved tolerability. This may allow patients to achieve optimal therapeutic doses and to benefit from a longer duration of treatment. [source] Cholinesterase inhibitors in advanced Dementia with Lewy bodies: increase or stop?INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2006Sanjeet Pakrasi Abstract Introduction There is little data on stopping cholinesterase inhibitors in Dementia with Lewy bodies (DLB). Equally, it is not known if increasing the dose of cholinesterase inhibitors may help neuropsychiatric symptoms in advanced DLB. Method We conducted an open label trial with donepezil involving 16 patients with LBD when the dose was reduced and treatment stopped over 4 weeks. Another 7 patients were given a trial of an increased dose of donepezil (15,mg) to resolve re-emergent neuropsychiatric symptoms. Results The slow discontinuation protocol was well tolerated in advanced DLB. Five of the seven patients given a trial of a higher dose of donepezil were rated as clinically improved after 12 weeks treatment. Conclusion Cholinesterase inhibitors can be discontinued slowly in advanced DLB. Increasing the dose of donepezil may be of benefit to some patients with DLB who experience a recurrence in their neuropsychiatric symptoms. Copyright © 2006 John Wiley & Sons, Ltd. [source] Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2005Peter J. Connelly Abstract Background Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. Methods A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). Results 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4,,139),=,5.60, p,<,0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p,<,0.05 in each case). This effect could not be explained by age or by smoking status. Conclusion Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome. Copyright © 2005 John Wiley & Sons, Ltd. [source] Cholinesterase inhibitors in the treatment of dementiaINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2003Maria Luisa Margallo-Lana No abstract is available for this article. [source] A Post-ischaemic Single Administration of Galanthamine, a Cholinesterase Inhibitor, Improves Learning Ability in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2000A. I. ILIEV Transient forebrain ischaemia is widely observed in clinical practice. We have examined the effect of a single administration of the Cholinesterase inhibitor galanthamine (2 mgkg,1, i.p.) 25 min after reperfusion in male Sprague-Dawley rats (180 ± 20 g) after a 20-min common carotid artery occlusion. Twenty-four-hours post-ischaemia there was no difference in motor co-ordination or muscle tonus of the rats treated with or without galanthamine as assessed by the rota-rod test. Learning ability was examined using the shuttle-box test, evaluating the latency time and the number of errors for six days in succession. The performance of the ischaemic saline-injected rats was significantly impaired on days 4, 5, 6 (latency time) compared with the non-ischaemic rats and with the ischaemic animals administered galanthamine (P< 0.05). Similar results were obtained when counting the number of errors (failure to cross the cage during conditioned or unconditioned stimulus). The monitoring of body temperature during the first 12-h post-ischaemia did not show any significant difference between the groups. The data showed a beneficial effect of galanthamine on the recovery of learning ability when administered once only post-ischaemia. This suggests a direct effect on the early pathologic mechanisms of CNS damage. Cholinesterase inhibitors may prove useful in the early clinical treatment of ischaemic conditions. [source] Event-related delta oscillatory responses of Alzheimer patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2008G. Yener Background and purpose:, Alzheimer type of dementia (AD) is the most common neuropsychiatric morbidity in elderly individuals. Event-related oscillations (ERO) provide an useful tool for detecting subtle abnormalities of cognitive processes with high temporal resolution. Methods:, In the present report, event-related oscillations of patients with AD were analyzed by using a visual oddball paradigm. A total of 22 mild probable AD subjects according to NINCDS-ADRDA criteria and 20 age-, gender-, and education-matched healthy control subjects were compared. AD group consisted from 11 untreated patients and 11 patients treated with cholinesterase inhibitor. Oscillatory responses were recorded from 13 scalp electrodes. Results:, Significant differences in delta frequency range were seen between the groups by using repeated measures of anova analysis [F(9.120) = 2.228; P = 0.022]. Post-hoc analyses using Wilcoxon test showed that at mid- and left central regions, (Cz, C3) peak amplitudes of delta responses of healthy subjects were significantly higher than either group. Also cholinesterase inhibitors did not have effect on delta oscillatory responses. Conclusions:, Our findings imply that the delta oscillatory responses at central locations are highly instable in mild probable AD patients regardless of treatment when compared to the healthy aged controls. This study supports the importance of oscillatory event-related potentials for investigating AD brain dynamics. [source] Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2006M. Mazza The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50,80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages. [source] Neostigmine and pilocarpine attenuated tumour necrosis factor , expression and cardiac hypertrophy in the heart with pressure overloadEXPERIMENTAL PHYSIOLOGY, Issue 1 2008Jessica Freeling The inflammatory cytokine tumour necrosis factor , (TNF,) is known to be a major factor contributing to cardiac remodelling and dysfunction. Parasympathetic nervous system cholinergic function can inhibit TNF, expression during systemic infection. In the present study, we tested the effects of a cholinesterase inhibitor, neostigmine, and a muscarinic cholinergic agonist, pilocarpine, on cardiac hypertrophy and TNF, levels during pressure overload. Rats with transverse aortic constriction exhibited elevated TNF, protein levels in the heart, increased heart weight to body weight ratios (an index of cardiac hypertrophy) and decreased left ventricular diastolic function. Two weeks of infusion with neostigmine (6 ,g kg,1 day,1) or pilocarpine (0.3 mg kg,1 day,1) significantly reduced cardiac hypertrophy, reduced TNF, levels and elevated interleukin-10 levels in heart tissues, and improved ventricular function in rats with transverse aortic constriction. Neither of these treatments significantly changed ventricular pressure load. Furthermore, in primary cultured neonatal cardiac cells, treatment with pilocarpine attenuated adrenergic agonist phenylephrine-induced increased TNF, expression and [3H]leucine (a marker of protein synthesis) incorporation in the cells. Collectively, both cholinergic agents decreased TNF, levels and attenuated cardiac hypertrophy. Since both agents potentially enhanced cholinergic function, the anti-inflammatory action may be involved in the cardioprotective effect of the treatments with these agents. [source] Donepezil Treatment of Topiramate-Related Cognitive DysfunctionHEADACHE, Issue 2 2006Steve D. Wheeler MD Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement. [source] Randomized double-blind placebo-controlled donepezil augmentation in antidepressant-treated elderly patients with depression and cognitive impairment: a pilot studyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2008Gregory H. Pelton Abstract Objective To assess combined antidepressant and cognitive enhancer treatment in elderly patients presenting with depression plus cognitive impairment. Methods Twenty-three elderly (>50 years old) depressed, cognitively impaired (DEP-CI) patients participated in a pilot study. We evaluated whether, after 8 weeks of open antidepressant treatment, donepezil HCl (Aricept) would afford added cognitive benefit compared to placebo in a randomized 12-week trial. A subsample continued in an 8-month extension phase of open treatment with donepezil. Neuropsychological testing (NPT) was performed and antidepressant response monitored at baseline and the 8, 20, and 52-week time points. Results At 8-weeks, the antidepressant response rate was 61% (14/23). Improvement in SRT immediate recall (SRT-IR; e.g. episodic verbal memory) was observed in responders compared to non-responders. During the 12-week, placebo-controlled, donepezil add-on trial, patients on donepezil showed further improvement in SRT-IR versus patients on placebo. In the open extension phase, patients who continued open donepezil treatment (n,=,6) maintained improvement in memory and tended to show an advantage over patients who never received donepezil and were evaluated at the 52-week time point (n,=,6). There were no observed significant donepezil effects on non-memory cognitive domains. Conclusion These preliminary findings suggest that addition of a cholinesterase inhibitor (AChEI) following antidepressant medication treatment in elderly Dep-CI patients may improve cognition, and support the need for a confirmatory, larger randomized placebo-controlled trial. Copyright © 2007 John Wiley & Sons, Ltd. [source] Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2005Peter J. Connelly Abstract Background Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. Methods A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). Results 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4,,139),=,5.60, p,<,0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p,<,0.05 in each case). This effect could not be explained by age or by smoking status. Conclusion Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome. Copyright © 2005 John Wiley & Sons, Ltd. [source] Treating the dementia of ,Iris' with a cholinesterase inhibitorINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 4 2003Peter J. Connelly No abstract is available for this article. [source] Post-operative pain relief following intrathecal injection of acetylcholine esterase inhibitor during lumbar disc surgery: a prospective double blind randomized studyJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2008Z. H. Khan MD Summary Background:, As spinal cholinergic receptors participate in the control of somatic pain, this effect could be potentiated by intrathecal injection of a cholinesterase inhibitor, neostigmine. Objective:, This study was designed to evaluate the effectiveness of intrathecal administration of neostigmine on pain relief after single level lumbar disectomy. Methods:, Sixty-six patients with unilateral extruded lumbar disc were randomly allocated into two groups, neostigmine (,N'), and control (,C'); the former received 100 ,g of neostigmine methylsulphate, whereas the latter received placebo intrathecally after termination of the surgery. Visual Analogue Scale was employed to measure post-operative pain, which was a primary outcome of the study. Opiate dosage consumed was also recorded as a primary outcome during the first 24 h following surgery. Nausea and vomiting although important were considered as secondary outcomes. Results:, Mean Visual Analogue Scale scores post-operatively at 1, 4 and 8 h were 2·24, 1·82 and 1·88 in group ,N' and 5·36, 5·61 and 4·88 in group C. Mean morphine used intravenously in the first 24 h was 0·9 mg in group ,N' and 4·7 mg in group C. All results were found to be significantly different in the two groups. The frequency of nausea and vomiting was not significantly different in the two groups ,C' (24%) and ,N' (18%). Conclusion:, Injection of 100 ,g hyperbaric neostigmine intrathecally was effective for pain relief, and reduced post-operative opiate demand. [source] Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5-HT4 receptor agonistNEUROGASTROENTEROLOGY & MOTILITY, Issue 11 2009K. Campbell-dittmeyer Abstract, Increased cholinergic stimulation and accelerated gastrointestinal (GI) transit may be produced by direct stimulation of the acetylcholine (ACh) receptor with an appropriate agonist by increased release of ACh from cholinergic nerve terminals or by a decreased removal or breakdown of ACh within cholinergic synapses. The acetylcholinesterase inhibitor, neostigmine, and the 5-HT4 receptor partial agonist tegaserod, are two agents with known prokinetic activity which work by different mechanisms that result in increased levels of ACh at cholinergic synapses innervating intestinal smooth muscle. Here, we aimed to investigate the potential synergistic effect on colonic transit that may occur with concomitant use of these two agents. Colonic transit was indirectly assessed in rats via measurements of fecal pellet output every 30 min for 2.5 h following administration of neostigmine (0.003,0.1 mg kg,1, i.p.), tegaserod (0.01,1.0 mg kg,1, i.p.), or a combination of both compounds. When administered alone, neostigmine or tegaserod caused a dose-dependent increase in fecal pellet output. In combination, low doses of the two agents which did not produce statistically significant effects alone, compared to the vehicle, caused a significant increase in fecal pellet output. Combinations of higher doses of neostigmine and tegaserod did not display synergy. In summary, when combined at low doses, neostigmine and tegaserod produce synergistic effects manifested by a statistically significant increase in the expulsion of fecal pellets. A combination of an anticholinesterase agent with a 5-HT4 receptor agonist may prove to be a useful therapeutic approach to treat conditions associated with slow GI transit. [source] Prevalence of cholinesterase inhibitors in subjects with dementia in Europe,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2008Antoine Pariente MD Abstract 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 © 2008 John Wiley & Sons, Ltd. [source] A review of studies describing the use of acetyl cholinesterase inhibitors in Parkinson's disease dementiaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2005I. D. Maidment Objective:, To review the literature relating to the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia (PDD). Method:, MEDLINE (1966 , December 2004), PsychINFO (1972 , December 2004), EMBASE (1980 , December 2004), CINHAL (1982 , December 2004), and the Cochrane Collaboration were searched in December 2004. Results:, Three controlled trials and seven open studies were identified. Efficacy was assessed in three key domains: cognitive, neuropsychiatric and parkinsonian symptoms. Conclusion:, Cholinesterase inhibitors have a moderate effect against cognitive symptoms. There is no clear evidence of a noticeable clinical effect against neuropsychiatric symptoms. Tolerability including exacerbation of motor symptoms , in particular tremor , may limit the utility of cholinesterase inhibitors. [source] Hippocampal structure and the action of cholinomimetic drugsDRUG DEVELOPMENT RESEARCH, Issue 3 2002John G. Csernansky Abstract Cholinomimetic drugs have become the clinical standard for the treatment of patients with dementia of the Alzheimer type (DAT). However, uncertainty remains as to the proportion of patients that respond to such drugs, and how one might predict the capacity for response before treatment is begun. The thesis of the present review is that the neuroanatomical integrity of the hippocampus determines, at least in part, the capacity of DAT patients to respond to cholinomimetic drugs. Neuroimaging studies suggest that volume losses and other neuroanatomical deformities of the hippocampus are common in patients with even mild DAT. Moreover, more severe neuroanatomical deformities of the hippocampus are associated with more severe dementia symptoms and more rapid clinical decline. Animal research, including studies of cholinergic antagonists, glutamatergic antagonists, hippocampal lesions, and animals with mutant amyloid precursor protein genes, demonstrate that behavioral abnormalities similar to those found in DAT patients, especially those related to memory, are associated with hippocampal pathology. Cholinomimetic drugs, in particular, the cholinesterase inhibitors, have been shown to reverse some but not all of these behavioral abnormalities. More research is needed in DAT patients to determine whether an analysis of hippocampal structure or function can reliably predict the outcome of treatment with cholinomimetic drugs. Further work in animals is also needed to determine the limitations of cholinomimetic drugs for reversing various types of cognitive deficits, and to develop and test other pharmacological strategies for the treatment of DAT. Drug Dev. Res. 56:531,540, 2002. © 2002 Wiley-Liss, Inc. [source] Cognitive enhancement as a pharmacotherapy target for stimulant addictionADDICTION, Issue 1 2010Mehmet Sofuoglu ABSTRACT Background No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. Aim To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Methods Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Results and conclusions Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha2 -adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction. [source] Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitorsEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010K. Schultz Background:, Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. Methods:, CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed for the presence of depression. Results:, No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors compared to those AD patients who were not. Conclusions:, Significant reductions in CSF TTR were found after cholinesterase inhibitor treatment in patients with AD compared to untreated individuals. CSF TTR was unaltered in patients with DLB and had no relationship to depression in the present cohort with dementias. [source] Event-related delta oscillatory responses of Alzheimer patientsEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2008G. Yener Background and purpose:, Alzheimer type of dementia (AD) is the most common neuropsychiatric morbidity in elderly individuals. Event-related oscillations (ERO) provide an useful tool for detecting subtle abnormalities of cognitive processes with high temporal resolution. Methods:, In the present report, event-related oscillations of patients with AD were analyzed by using a visual oddball paradigm. A total of 22 mild probable AD subjects according to NINCDS-ADRDA criteria and 20 age-, gender-, and education-matched healthy control subjects were compared. AD group consisted from 11 untreated patients and 11 patients treated with cholinesterase inhibitor. Oscillatory responses were recorded from 13 scalp electrodes. Results:, Significant differences in delta frequency range were seen between the groups by using repeated measures of anova analysis [F(9.120) = 2.228; P = 0.022]. Post-hoc analyses using Wilcoxon test showed that at mid- and left central regions, (Cz, C3) peak amplitudes of delta responses of healthy subjects were significantly higher than either group. Also cholinesterase inhibitors did not have effect on delta oscillatory responses. Conclusions:, Our findings imply that the delta oscillatory responses at central locations are highly instable in mild probable AD patients regardless of treatment when compared to the healthy aged controls. This study supports the importance of oscillatory event-related potentials for investigating AD brain dynamics. [source] Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2006M. Mazza The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50,80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages. [source] Withanoside IV and its active metabolite, sominone, attenuate A,(25,35)-induced neurodegenerationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Tomoharu Kuboyama Abstract At the present, medication of dementia is limited to symptomatic treatments such as the use of cholinesterase inhibitors. To cure dementia completely, that is regaining neuronal function, reconstruction of neuronal networks is necessary. Therefore, we have been exploring antidementia drugs based on reconstructing neuronal networks in the damaged brain and found that withanoside IV (a constituent of Ashwagandha; the root of Withania somnifera) induced neurite outgrowth in cultured rat cortical neurons. Oral administration of withanoside IV (10 µmol/kg/day) significantly improved memory deficits in A,(25,35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 µm) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 µm A,(25,35). These data suggest that orally administrated withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after metabolism is sominone. [source] Treatment of behavioural symptoms and dementia in Parkinson's diseaseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2005Hasmet A. Hanagasi Abstract Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD. [source] | |||||||||||||||||||||||||||||||