Review of the acetylcholinesterase inhibitor galanthamine

Galantamine hydrobromide is a tertiary alkaloid drug that has been developed and approved in a number of countries including the USA and several countries in Europe as a treatment for mild-to-moderate Alzheimer's disease (AD). Galantamine has a unique, dual mode of action. It is a reversible, competitive inhibitor of acetylcholinesterase (AChE), and is the only drug actively marketed for the treatment of AD with proven activity as an allosteric modulator of nicotinic acetylcholine receptors (nAChRs). This latter activity is thought to be particularly important since decreases in the expression and activity of nAChRs make a large contribution to the reduction in central cholinergic neurotransmission in patients with AD. Galantamine exhibits favorable pharmacokinetic characteristics including predictable linear elimination kinetics at the recommended maintenance doses (16 and 24 mg/day), a relatively short half-life (approximately 7 h) and high bioavailability. It is extensively metabolized in numerous pathways, mainly in the liver via cytochrome P450 enzymes CYP2D6 and CYP3A4, and has a low potential for clinically significant drug-drug interactions. During four large randomized, double-blind, placebocontrolled trials of up to 6 months duration, galantamine 16 and 24 mg/day significantly benefited cognitive and global function, ability to perform activities of daily living (ADL) and behavior, relative to placebo and baseline, for up to 6 months. Caregiver burden (time spent by caregivers supervising patients or assisting them with ADL), and caregiver distress (related to patients' behavioral symptoms) were also reduced. Cognitive and functional abilities were preserved at or near baseline for at least 12 months in patients who re- 159CNS Drug Reviews Vol. 8, No.2, pp. 159-176 © 2002 Neva Press, Branford, Connecticut Address correspondence and reprint requests to: Sean Lilienfeld, MBBCh, FCP(SA), MMed(Neuro), Janssen Pharmaceutica Inc, Janssen Research Foundation, Div of Janssen Pharmaceutica Ltd, 1125 Trenton Harbourton Road, Titusville NJ 08560. Tel.: +1 (609) 730-3414; Fax: +1 (609) 730-2441; E-mail: slilien1@janus.jnj.com ceived galantamine 24 mg/day for 12 months in a long-term US study. These benefits were maximized by early and continued galantamine treatment and, again, were associated with significant reductions in caregiver burden. Trials of the efficacy of galantamine in dementia related to cerebrovascular disease have also yielded positive results. There are no safety concerns associated with the use of galantamine. The incidence of adverse events, particularly cholinergically mediated events affecting the gastrointestinal system, is generally low and can be minimized using the recommended slow dose-escalation scheme. Galantamine may, therefore, help to reduce the overall burden and cost involved in caring for dementia patients. Taking all evidence into account, galantamine has the potential to become a first-line therapy for dementia.

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“…It has also been isolated from the bulbs of the common snowdrop and several Amaryllidaceae plants (53). The chemical name of galantamine ( Fig.…”

Section: Chemistrymentioning

confidence: 99%

Galantamine — a Novel Cholinergic Drug with a Unique Dual Mode of Action for the Treatment of Patients with Alzheimer's Disease

2002

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“…47) Selective loss of cholinergic neurons and decrease in cholinacetyltransferase activity was reported to be a characteristic feature of senile dementia of the Alzheimer's type. 48) Anticholinesterases such as Metrifonate, 49) Physostigmine, Tacarine, Donepezil, 50) Huperzine-A, 51) Rivastigmine, 52) Galanthamine 53) and Eptastigmine 54) have all been shown to reverse amnesia produced by disruption of cholinergic system. Enzyme choline acetyltransferase is involved in the synthesis of acetylcholine and acetylcholinesterase is involved in the degradation of acetylcholine.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Evidence for the Potential of Daucus carota in the Management of Cognitive Dysfunctions

Mani

Parle

2006

Biological & Pharmaceutical Bulletin

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Cognition is that operation of mind by means of which, we become aware of our surroundings, objects and thoughts. Alzheimer's disease (AD) represents the most common cause of dementia, affecting more than 15 million individuals worldwide.1) It is characterized by progressive memory loss, cognitive impairments, and personality defects accompanied by diffuse structural abnormalities in the brain.2,3) Memory forms one of the most complex functions of the brain and ultimately involves multiple neuronal pathways and neurotransmitter systems. One of the most consistent and profound change associated with AD is diminished central cholinergic neurotransmission.4) Therefore, facilitation of cholinergic transmission by inhibition of acetyl cholinesterase enzyme can be looked upon as an important strategy in improving cognitive and behavioral functions.2) The main histological hallmarks of AD are extraneuronal deposits of b-amyloid (Ab) plaques and intra neuronal fibrillary tangles. 5) Recently, substantial evidence is accumulating in the literature showing a strong link between high cholesterol and high incidence of Alzheimer's disease. [5][6][7] Both the generation and clearance of Ab appear to be regulated by cholesterol. Elevated cholesterol levels increased Ab in cellular and most animal models of AD whereas, drugs that inhibited cholesterol synthesis lowered Ab.6) Clinical studies indicated that patients with elevated serum cholesterol levels have increased susceptibility to AD, [8][9][10][11] and that the prevalence of AD is higher in countries with high-fat intake.12) Therefore, a new approach aimed at reducing blood cholesterol level may prove worthwhile in the management of Alzheimer's disease. Since the Allopathic system of medicine is yet to provide a radical cure for Alzheimer's disease, it is worthwhile to look for new directions, which would minimize the memory loss of patients with neuropsychiatric disorders. The utility of non-toxic plants may be explored for treating patients with dementia.Daucus carota LINN. commonly known as "Carrot" belongs to the family Apiaceae (Umbelliferae) and is cultivated almost all over the world as a useful vegetable. Different parts of this plant are used in Indian systems of medicine for the treatment of a broad spectrum of aliments including kidney dysfunction, asthma, dropsy, inflammation, leprosy and worm troubles. 13,14) The plant has undergone extensive phytochemical studies and a large number of active ingredients have been isolated. These include volatile oils, steroids, triterpenes, carbohydrates, glycerides, tannins, flavonoids, amino acid, carotene and hydrocarotene. [15][16][17] Pharmacological studies showed that Daucus carota seeds exhibit antifertility properties. 18,19) The crude extract of root of the plant has been found to be hypoglycemic 20) and hepatoprotective.21) Indian Materia Medica makes a mention of Daucus carota seeds as a brain tonic.14) Cholinergic activity was also found in water-soluble fraction of the alcoholic extract of seeds.22,23) Since, D...

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“…이 중 가장 많은 비율을 차지하는 Alzheimer's disease(AD)는 뇌의 전반적 위축과 특 유의 조직학적 소견을 나타내며 4) AD는 뇌 안에서 뉴론 (neuron)의 점차적인 퇴화와 손실이 특징인 연령과 관계된 신경퇴화 질병이다 5) . AD의 주증상인 기억력 감퇴는 choline 성 신경계와 밀접한 관계가 있다고 알려져 있는데, 특히 choline성 신경세포의 퇴화에 의한 Acetylcholine의 부족 때 문으로 생각되며, 이러한 현상은 Acetylcholine의 분해효소인 Acetylcholinesterase(AChE)의 증가로 더욱 심화된다 6) . 또 대다수의 치매환자는 각종 증상이 수반되는 복합병변으로 인 해 심적 부담을 느껴 우울증에 시달리기도 한다.…”

Section: 서 론 1)2)unclassified

A Comparative Study of Memory Improving Effects of Taraxaci herba on Scopolamine-induced Amnesia in Mouse

Sohn¹,

Shin²

2012

The Korea Journal of Herbology

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Objectives : The purpose of this study was to characterize the effect of the fraction of Taraxacum officinale and T.coreanum on the learning and memory impairments induced by scopolamine. Methods : The cognition-enhancing effect of Taraxacum officinale and T.coreanum was investigated using a passive avoidance test, the Morris water maze test and Y-maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.).Results : The results showed that the Aug harvested T.offiicinale extract-treated group (200 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Passive avoidance Y-maze test and Watermaze test. And these results are same manner in DPPH radical scavenger effect and Acetylcholineseterase inhibition effect. Conclusions : These results suggest that Taraxacum officinale extract maybe a useful cognitive impairment treatment, and its beneficial effects are depending on the collecting time and origin plants. As a result, Taraxacum officinale harvested in August improve memory most.

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Review of the acetylcholinesterase inhibitor galanthamine

Cited by 158 publications

References 32 publications

Galantamine — a Novel Cholinergic Drug with a Unique Dual Mode of Action for the Treatment of Patients with Alzheimer's Disease

Galantamine — a Novel Cholinergic Drug with a Unique Dual Mode of Action for the Treatment of Patients with Alzheimer's Disease

Pharmacological Evidence for the Potential of Daucus carota in the Management of Cognitive Dysfunctions

A Comparative Study of Memory Improving Effects of Taraxaci herba on Scopolamine-induced Amnesia in Mouse

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