Galantamine hydrobromide

The bulbs of Lycoris radiata

Long-acting, centrally active acetylcholinesterase inhibitor (IC50 = 410 nM) and allosteric potentiator at neuronal nicotinic ACh receptors. Prevents β-amyloid-induced apoptosis in SH-SY5Y and bovine chromaffin cells. Long-term administration reduces amyl

The effects of galantamine hydrobromide treatment on dehydroepiandrosterone sulfate and cortisol levels in patients with chronic fatigue syndrome.[Pubmed:20046396]

Psychiatry Investig. 2009 Sep;6(3):204-10.

OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic neurotransmission may cause the hypothalamic-pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the alterations in stress hormones such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4-week administration of Galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate whether there are any relationships between the probable hormonal changes and cholinergic treatment. METHODS: Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the patient group, four weeks after 8 mg/d Galantamine hydrobromide treatment, cortisol and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were divided into two subgroups as responders and nonresponders according to the reduction in their Newcastle Research Group ME/CFS Score Card (NRG) scores. RESULTS: Important findings of this study are lower pre-and post-treatment cortisol levels and in all CFS patients compared to controls (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher DHEAS/cortisol molar ratios which were normalized following four weeks' treatment with 8 mg/d Galantamine hydrobromide in the treatment-respondent group (F=5.382, p=0.029; F=5.722, p=0.025, respectively). CONCLUSION: The findings of the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit hypothesis in CFS.

Stability-indicating study of the anti-Alzheimer's drug galantamine hydrobromide.[Pubmed:21300511]

J Pharm Biomed Anal. 2011 Apr 28;55(1):85-92.

Galantamine hydrobromide was subjected to different stress conditions (acidic, alkaline, thermal, photolytic and oxidative). Degradation was found to occur under acidic, photolytic and oxidative conditions, while the drug was stable under alkaline and elevated temperature conditions. A stability-indicating reversed-phase liquid chromatographic method was developed for the determination of the drug in the presence of its degradation products. The method was validated for linearity, precision, accuracy, specificity, selectivity and intermediate precision. Additionally, the degradation kinetics of the drug was assessed in relevant cases. The kinetics followed a first order behavior in the case of acidic and photolytic degradation, while a two-phase kinetics behavior was found for the oxidative degradation. The degradation products were characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. Dehydration, epimerization and N-oxidation were the main processes observed during the degradation of galantamine. Moreover, if sufficient material could be isolated the inhibitory activity against the target enzyme acetylcholinesterase was also assessed.

Development and in vivo evaluation of novel monolithic controlled release compositions of galantamine hydrobromide as against reservoir technology.[Pubmed:21770841]

Pharm Dev Technol. 2013 Sep-Oct;18(5):1148-58.

The objective of this study is to develop and in vivo evaluation of novel monolithic matrix mini tablets approach to control the release of Galantamine hydrobromide (GAH) in comparison with desired release profile to the Innovator formulation Razadyne((R)) ER capsules. The direct compression method was employed for preparation of matrix mini tablets as against reservoir multiparticulate pellets of innovator formulation. The matrix swellings, dissolution similarity, mean dissolution time and dissolution efficiency of formulations were evaluated. It was found that increase in the concentration of high viscosity hydroxypropylcellulose (HPC) results reduction in release rate. The drug release was shown to be pH dependent with faster rate at lower pH. The release of GAH followed first order shifting to dissolution dependent by increase of HPC content. The formulation showed stability of drug release. In vivo prediction was done by Wagner-Nelson method. Prediction errors were estimated for Cmax and area under curve (AUC) and found to be not exceeding 15%. In vivo study in human volunteers confirmed the similarity between test and innovator formulations and pharmacokinetic values were comparable between actual and predicted. These results suggest that novel monolithic matrix approach could be suitable technique to formulate controlled release GAH.

Galantamine prevents apoptosis induced by beta-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors.[Pubmed:14654102]

Neuropharmacology. 2004 Jan;46(1):103-14.

Galantamine is currently used to treat Alzheimer's disease patients; it behaves as a mild blocker of acetylcholinesterase (AChE) and has an allosteric modulating action on nicotinic acetylcholine receptors (nAChRs). In this study, we observed that galantamine prevented cell death induced by the peptide beta-amyloid(1-40) and thapsigargin in the human neuroblastoma cell line SH-SY5Y, as well as in bovine chromaffin cells. The protective effect of galantamine was concentration-dependent in both cell types; maximum protection was produced at 300 nM. The antiapoptotic effect of galantamine at 300 nM, against beta-amyloid(1-40) or thapsigargin-induced toxicity, was reversed by alpha-bungarotoxin. At neuroprotective concentrations, galantamine caused a mild and sustained elevation of the cytosolic concentration of calcium, [Ca2+]c, measured in single cells loaded with Fura-2. Incubation of the cells for 48 h with 300 nM galantamine doubled the density of alpha7 nicotinic receptors and tripled the expression of the antiapoptotic protein Bcl-2. These results strongly suggest that galantamine can prevent apoptotic cell death by inducing neuroprotection through a mechanism related to that described for nicotine, i.e. activation of nAChRs and upregulation of Bcl-2. These findings might explain the long-term beneficial effects of galantamine in patients suffering of Alzheimer's disease.

Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors.[Pubmed:12649296]

J Pharmacol Exp Ther. 2003 Jun;305(3):1024-36.

Galantamine (Reminyl), an approved treatment for Alzheimer's disease (AD), is a potent allosteric potentiating ligand (APL) of human alpha 3 beta 4, alpha 4 beta 2, and alpha 6 beta 4 nicotinic receptors (nAChRs), and of the chicken/mouse chimeric alpha 7/5-hydroxytryptamine3 receptor, as was shown by whole-cell patch-clamp studies of human embryonic kidney-293 cells stably expressing a single nAChR subtype. Galantamine potentiates agonist responses of the four nAChR subtypes studied in the same window of concentrations (i.e., 0.1-1 microM), which correlates with the cerebrospinal fluid concentration of the drug at the recommended daily dosage of 16 to 24 mg. At concentrations >10 microM, galantamine acts as an nAChR inhibitor. The other presently approved AD drugs, donepezil and rivastigmine, are devoid of the nicotinic APL action; at micromolar concentrations they also block nAChR activity. Using five CHO-SRE-Luci cell lines, each of them expressing a different human muscarinic receptor, and a reporter gene assay, we show that galantamine does not alter the activity of M1-M5 receptors, thereby confirming that galantamine modulates selectively the activity of nAChRs. These studies support our previous proposal that the therapeutic action of galantamine is mainly produced by its sensitizing action on nAChRs rather than by general cholinergic enhancement due to cholinesterase inhibition. Galantamine's APL action directly addresses the nicotinic deficit in AD.

Nerve growth factor and galantamine ameliorate early signs of neurodegeneration in anti-nerve growth factor mice.[Pubmed:12205295]

Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12432-7.

Phenotypic knockout of nerve growth factor (NGF) activity in transgenic anti-NGF mice (AD11 mice) results in a progressive neurodegenerative phenotype resembling Alzheimer's disease. In this article, we examine whether and how the progressive neurodegenerative phenotype of AD11 mice could be prevented or ameliorated by pharmacological treatments with NGF or the cholinergic agonist galantamine, at a relatively early phase of Alzheimer's disease-like neurodegeneration. We demonstrate that the neurodegeneration induced by the expression of anti-NGF antibodies in AD11 mice can be largely reversed by NGF delivery through an olfactory route.

The pharmacology of galanthamine and its analogues.[Pubmed:8604434]

Pharmacol Ther. 1995;68(1):113-28.

Galanthamine is an alkaloid found in the bulbs of snowdrops and several Amaryllidaceae plants. At submicromolar concentrations, it inhibits acetylcholinesterase activity, but it is much less potent against butyrylcholinesterase activity. Galanthamine has been used in anaesthetics to reverse neuromuscular paralysis by tubocurarine-like muscle relaxants, but it is a tertiary amine that gets into the brain to cause central effects. Galanthamine is being studied as a possible therapeutic agent in Alzheimer's disease because of its central cholinergic effects. Positive effects have been demonstrated in several learning and memory tests in animals.

Galanthamine, an acetylcholinesterase inhibitor: a time course of the effects on performance and neurochemical parameters in mice.[Pubmed:2626444]

Pharmacol Biochem Behav. 1989 Sep;34(1):129-37.

The time course of the effects of the long-acting acetylcholinesterase (AChE) inhibitor, galanthamine, on a spatial navigation task and on AChE and acetylcholine (ACh) levels were investigated in mice. Mice received either saline or ibotenic acid injections into the nucleus basalis magnocellularis (nBM). The control and nBM group were than trained to perform a modified Morris swim task and the time to find the hidden platform was recorded. The nBM group took significantly longer to find the platform than the control group in the reversal phase of testing. Galanthamine attenuated the performance deficit in the nBM-lesioned group in a time-dependent manner, with peak performance at four hours after injection of 5.0 mg/kg galanthamine IP. This dose impaired performance of the task in control mice, with the most severe deficits observed at two hours after injections when motor activity was severely reduced. Galanthamine (5.0 mg/kg IP) significantly decreased cortical AChE activity and significantly increased cortical ACh content in control mice in a time-dependent manner. The time courses of the neurochemical effects, however, did not correlate precisely with the behavioral time course. Galanthamine concentrations up to 1 x 10(-5) M did not affect choline acetyltransferase (ChAT) activity, [3H]hemicholinium-3 (HCh-3) binding to the choline carrier, [3H]quinuclidinylbenzilate (QNB) binding to muscarinic receptors, or [3H]acetylcholine binding to nicotinic receptors in cortical homogenates. AChE activity was inhibited by galanthamine in cortical homogenates with an IC50 of 4.1 x 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Galanthamine hydrobromide is a long-acting, centrally active acetylcholinesterase(AChE) inhibitor (IC50 = 410 nM) and allosteric potentiator at neuronal nicotinic ACh receptors.

Galantamine hydrobromide,1953-04-4,Galantamine hydrobromide;69353-21-5;193146-85-9,Natural Products,AChR, buy Galantamine hydrobromide , Galantamine hydrobromide supplier , purchase Galantamine hydrobromide , Galantamine hydrobromide cost , Galantamine hydrobromide manufacturer , order Galantamine hydrobromide , high purity Galantamine hydrobromide