The Case of Galantamine: Repurposing and Late Blooming of a Cholinergic Drug

Mucke, Hermann Am

doi:10.4155/fso.15.73

Cited by 53 publications

(20 citation statements)

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“…It also potentiated the discriminative effect of nicotinic agonists (Mohler et al , ). The nAChR PAM galantamine is an FDA approved drug for Alzheimer's disease (Mucke, ) and galantamine is also an acetylcholinesterase inhibitor that increases activation of nAChRs by increasing the concentration and duration of ACh. The PAM dFBr relieves the inhibition of α2β2 and α4β2 nAChRs by Aβ(1–42) peptide, which forms the amyloid characteristic of Alzheimer's disease (Pandya and Yakel, ).…”

Section: Introductionmentioning

confidence: 99%

Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors

Wang

Lindstrom

2017

British J Pharmacology

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Section: Introductionmentioning

confidence: 99%

Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors

Wang

Lindstrom

2017

British J Pharmacology

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“…Whereas, a new drug candidate takes billion of dollars and at least 15 years to come in the market [ 8 ]. In fact, one of the establish drug for AD, Galanthamine, an acetylcholinesterase (AChE) inhibitor was earlier used for Poliomyelitis in Eastern Europe and then repurposed for use in AD same as Lundbeck repurposed memantine for therapeutic use in AD as Ebixa ® [ 9 , 10 ]. Other examples include citalopram, desvenlafaxine, and fluoxetine (Selective Serotonin Reuptake Inhibitors), levetiracetam (antiepileptic drug), perindopril, nilvadipine, carvedilol (antihypertensive drugs), liraglutide, lixisenatide, metformin, exenatide (anti-diabetes drugs) all have shown to be significant in AD [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

In silico repurposing of antipsychotic drugs for Alzheimer’s disease

2017

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BackgroundAlzheimer’s disease (AD) is the most prevalent form of dementia and represents one of the highest unmet requirements in medicine today. There is shortage of novel molecules entering into market because of poor pharmacokinetic properties and safety issues. Drug repurposing offers an opportunity to reinvigorate the slowing drug discovery process by finding new uses for existing drugs. The major advantage of the drug repurposing approach is that the safety issues are already investigated in the clinical trials and the drugs are commercially available in the marketplace. As this approach provides an effective solution to hasten the process of providing new alternative drugs for AD, the current study shows the molecular interaction of already known antipsychotic drugs with the different protein targets implicated in AD using in silico studies.ResultA computational method based on ligand–protein interaction was adopted in present study to explore potential antipsychotic drugs for the treatment of AD. The screening of approximately 150 antipsychotic drugs was performed on five major protein targets (AChE, BuChE, BACE 1, MAO and NMDA) by molecular docking. In this study, for each protein target, the best drug was identified on the basis of dock score and glide energy. The top hits were then compared with the already known inhibitor of the respective proteins. Some of the drugs showed relatively better docking score and binding energies as compared to the already known inhibitors of the respective targets. Molecular descriptors like molecular weight, number of hydrogen bond donors, acceptors, predicted octanol/water partition coefficient and percentage human oral absorption were also analysed to determine the in silico ADME properties of these drugs and all were found in the acceptable range and follows Lipinski’s rule.ConclusionThe present study have led to unravel the potential of leading antipsychotic drugs such as pimozide, bromperidol, melperone, anisoperidone, benperidol and anisopirol against multiple targets associated with AD. Benperidol was found to be the best candidate drug interacting with different target proteins involved in AD.

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“…In fact, this alkaloid, present in Galanthus sp., aroused interest when it was found that it could inhibit muscle acetylcholinesterase, being a good candidate for treating myopathies and peripheral neuropathies, and for the reversal of neuromuscular blockade after anaesthesia, due to the capability of galantamine ( 1 ) to enhance nerve impulse transmission. As it has a tertiary ammonium base, galantamine ( 1 ) can easily penetrate the blood-brain barrier and inhibit brain acetylcholinesterase, which makes it particularly interesting [ 17 , 18 ]. In the 1980s, the therapeutic effects of galantamine started being studied for the treatment of AD, and its introduction in the anti-Alzheimer’s armamentarium was made in the year 2000; it still remains one of the most used drugs for delaying the appearance of severe symptoms in patients suffering from AD [ 18 ].…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

Old Drugs as New Treatments for Neurodegenerative Diseases

2018

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Neurodegenerative diseases are increasing in number, given that the general global population is becoming older. They manifest themselves through mechanisms that are not fully understood, in many cases, and impair memory, cognition and movement. Currently, no neurodegenerative disease is curable, and the treatments available only manage the symptoms or halt the progression of the disease. Therefore, there is an urgent need for new treatments for this kind of disease, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years. New therapies can come from three main sources: synthesis, natural products, and existing drugs. This last source is known as drug repurposing, which is the most advantageous, since the drug’s pharmacokinetic and pharmacodynamic profiles are already established, and the investment put into this strategy is not as significant as for the classic development of new drugs. There have been several studies on the potential of old drugs for the most relevant neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

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The Case of Galantamine: Repurposing and Late Blooming of a Cholinergic Drug

Cited by 53 publications

References 20 publications

Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors

Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors

In silico repurposing of antipsychotic drugs for Alzheimer’s disease

Old Drugs as New Treatments for Neurodegenerative Diseases

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