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Background Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment so far. Our study aimed to evaluate the potential anti-CHIKV activity of memantine hydrochloride (mtnH), a drug from the class of the aminoadamantanes approved for the treatment of Alzheimer´s disease, as a possible drug to be repurposed to the treatment of Chikungunya fever. Methods MtnH antiviral activity against CHIKV was determined by infecting BHK-21 cells with CHIKV-nanoluc, a virus carrying the marker nanoluciferase reporter, in the presence or absence of mtnH at concentrations ranging from 500 to 1.45 µM. The effective concentration of 50% inhibition (EC50) was calculated. Cell viability assay (determination of CC50) was also performed employing BHK-21 cells. Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay (Ames test). Results MtnH presented a CC50 of 248.4 ± 31.9 µM and an EC50 of 32.4 ± 4 µM against CHIKV in vitro. The calculated selectivity index (SI) was 7.67. MtnH did not induce genetic mutation in Salmonella strains with or without an external metabolizing system. Conclusion With the data herein presented, it is possible to hypothesize mtnH as a viable candidate to be repurposed as an anti-CHIKV drug. Clinical assays are, therefore, encouraged due to the promising in vitro results. Graphic abstract The drug memantine hydrochloride is herein personified with a doubt: as a prior regulated drug against Alzheimer, could it follow the path against Chikungunya virus too?

Purpose Memantine is currently the only drug that acts on the glutamate energy system to treat Alzheimer's disease. A generic memantine tablet was developed to offer an alternative to the marketed tablet formulation. The purpose of this study was to assess the bioequivalence of two different memantine formulations among healthy male Chinese subjects under fasting and fed conditions. Materials and methods We carried out single-center, randomized, single-dose, open-label, two-period, cross-over studies which including 20 healthy male Chinese subjects under fasting and fed conditions, respectively. Plasma samples were collected prior to and up to 240 hours after dosing. Key pharmacokinetic parameters including area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t), area from time zero to infinite (AUC0-∞), and Cmax were used for bioequivalence assessment. Results Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference drug for memantine were 106.5 - 114.0% for Cmax, 99.4 - 107.9% for AUC0-t, and 100.0 - 109.6% for AUC0-∞. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference drug for memantine were 94.8 - 104.3% for Cmax, 98.2 - 110.5% for AUC0-t, and 99.2 - 113.0% for AUC0-∞. Conclusion The observed pharmacokinetic parameters of memantine of the test drug were similar to those of the reference formulation both in the fasting and fed state. That is to say, the test formulation of memantine 10-mg tablet is bioequivalent to the reference formulation (Ebixa 10-mg tablet).

Memantine is an acetylcholine esterase and monoamine oxidase inhibitor used to treat Alzheimer’s and Parkinson’s diseases. Galanthamine, Rivastigmine, Donepezil, and Memantine are the most commonly...

Objective: The study is directed towards the development of an orally disintegrating drug delivery system of memantine hydrochloride which can be commercially exploited for the well-being of society for the treatment of Alzheimer’s disease, which is a most common form of dementia. Methods: Orally disintegrating immediate-release tablets of memantine hydrochloride were prepared and optimized for disintegration time and in vitro drug release. The top spray granulation method was used for the preparation of granules. Subsequently, these granules were compressed to tablets. The levels of diluent, disintegrant and taste-masking agents were optimized using the design of experiments. The resulting tablets were evaluated for disintegration time and in vitro drug release. The optimized formulation was subjected to accelerated stability study for 3 mo. Results: The optimized orally disintegrating tablet formulation exhibited a disintegration time of 2-3 min and complete drug release i.e. more than 85 % drug release within 10 min while performing in vitro drug release study. This is a prerequisite for faster action in the case of patients suffering from Alzheimer’s disease. Accelerated stability studies indicated good physical and chemical stability of the optimized formulation. Conclusion: Developed orally disintegrating tablet formulation of memantine hydrochloride could release the drug faster compared to conventional immediate-release tablets which is useful in paediatric, geriatric and psychiatric patients.

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P P P P Conclusions Taken together, these data supported the notion that CG combined with Mm might ameliorate the cognitive impairment through multiple pathways, suggesting that CG could play a role as complementary medicine to increase anti-AD effect of chemical drugs by reducing Aβ deposition, neuroinflammation, oxidative damage, and improving synaptic plasticity.

A selective, new, rapid and nondestructive Fourier transform Infrared spectroscopic assay has been developed for simultaneous determination of Memantine hydrochloride and Amisulpride in human plasma and their pharmaceutical formulations without interference from common dugs excipients. A binary mixture of ME and nonselective β-blocker namely; carvidalol has been determined the solid-state by FTIR spectroscopy for the first time. The linear range had been extent from 1.0 to 8.0 and 1.0 to 10.0 μg/mg, for ME and AMS respectively. The detection limits were 0.29 and 0.23 μg/mg while quantitation limits were 0.90 and 0.71 μg/mg for ME and AMS respectively. The developed assay has been validated according to ICH & USP recommendations and successfully applied for quantitative determination of selected drugs in biological fluid.

Effects of course (5 days) peroral introductions of memantine on behavioral indices of rafts in the open field test were examined. Ten animals were divided into two groups, control and experimental; rats of the latter group obtained five everyday introductions of 20 mg/kg memantine hydrochloride. Animals of the experimental group demonstrated more intense orientational/research activity (number of rearings) and significantly greater number of goings to the arena center. The dynamics of nearly all indices shown by rats of the two groups were dissimilar; memantine noticeably modified the structure of grooming behavior. Behavioral patterns in the open field allow one to conclude that memantine induces significant decreases in the levels of anxiety and fear. In general, effects of this agent can be characterized as adaptational/stimulatory ones. [1, 2]

Alzheimer's disease is the most common cause of dementia, affecting more than 48 million people worldwide. It has been predicted that by 2050 this figure will be more than 130 million.1 Alzheimer's...

Accurate, simple, sensitive, and fast spectrophotometric assay was applied for the quantification of certain anti-Alzheimer drug namely; Memantine hydrochloride, in its bulk and pharmaceutical preparation. The described assay has been established on the reaction between the primary amino moiety of the cited drug and 2,2-dihydroxyindane-1,3-dione reagent in N,N′-dimethylformamide medium in boiling water bath. Which give Ruhemann’s purple color that can be determined at λmax = 595 nm. Beer’s law has been obeyed within drug concentration range from 10-120 μg per milliliter. Detection limit and quantitation limit have been 1.6 & 4.9 μg per milliliter respectively. Developed procedure has been validated in agreement with International Conference of Horizon recommendations and applied successfully for detection of cited drug in bulk, pharmaceutical dosage form and content uniformity testing.

A new, selective and accurate spectrofluorimetric assay has been described for detection of Amisulpride and Memantine hydrochloride in pharmaceutical formulations and real plasma samples. The described assay depends on the reaction between the primary amino group of the selected drugs with acetyl acetone & formaldehyde in an acetate buffer of pH4.8. The derivatized product showed yellow fluorescence at λex=418nm and λem=484.5nm. The calibration graph was linear in the range of 0.05-0.5 and 0.2-1μgmL-1 for AMS and ME, orderly. The limits of detection were 0.0085 and 0.0153μgmL-1, and the limits of quantitation were 0.026 and 0.0464μgmL-1 for AMS and ME respectively. Validation of the described assay was in consonance with ICH guideline. Due to the sensitivity of the prescribed assay, it permits the determination of selected medications in biological sample quantitatively.

A simple, accurate and cost-effective ultraviolet-high performance liquid chromatography (UV-HPLC) assay method was developed and validated for the determination of derivatized memantine, a representative oral noncompetitive N-methyl-d-aspartate receptor antagonist to treat Alzheimer’s disease, in dissolution medium. Optimized derivatization process of memantine was performed with 9-fluorenylmethyl-chloroformate (FMOC), and injected with the UV-HPLC system for quantitation. Derivatized memantine were separated on a reverse phase C18 column (Shiseido, 250 × 4.6 mm, 5 μm) with a mixture of 50 mM phosphate buffer (pH 4, adjusted with orthophosphoric acid) and Acetonitrile (20:80, v/v), at a flow rate of 2.0 mL/min. UV detection was monitored at 265 nm. The detector response was specific and linear over the concentration range of 1.0–20.0 μg/mL. Validation parameters of derivatized memantine with the sensitivity, selectivity, linearity, accuracy, precision and stability in dissolution medium (pH 1.2) were acceptable based on International Conference on Harmonization Q2 (R1). The assay method validated in this work was successfully applied for a dissolution study of a commercial tablet containing memantine hydrochloride (i.e., Ebixa®, 10 mg). Thus, the developed method would be appropriate for routine in vitro dissolution studies of memantine hydrochloride tablet.

In people with moderate-to-severe dementia in Alzheimer's disease (AD) memantine provides some clinical benefits. It is commonly administered twice daily at a maximum dose of 20 mg. To improve medication adherence, convenience of use and to enable a higher daily dose, a 28 mg, extended-release formulation of memantine has been developed.We review the results of a Phase III randomized and controlled trial of memantine extended release as an add-on treatment and compared the findings with a similarly designed previous trial evaluating the immediate release (IR) form.Memantine extended release produced minor benefits on cognitive ability, including verbal fluency, behavioral problems and global clinical assessment. There was no difference between the treatment groups on activities of daily living. The observed effects were not larger than those of the IR formulation tested in a similar setting. The lack of impact on activities of daily living suggests that the small improvements in cognition and behavior did not translate into clinically important changes. In conclusion, there is no convincing evidence that the novel once-daily formulation of memantine represents a significant progress in the clinical management of AD that would justify additional treatment costs.

In November 2006 the National Institute for Health and Clinical Excellence (NICE) published the final review of its guidance on the use of anticholinesterase drugs and memantine hydrochloride for the treatment of Alzheimer's disease. Recommendations included a reduction in the use of anticholinesterase drugs, limiting them to the treatment of patients in the moderate-to-severe stages of the disease and an end to the use of memantine for newly diagnosed patients. This article examines the impact of this NICE decision on those people suffering from Alzheimer's disease and their carers and families.

A fully automated sequential injection analysis (SIA) method for chemiluminescence (CL) determination of Al-zheimer's drug memantine hydrochloride was developed and presented. The employing of SIA injection analysis facilitates fluidic handling and lowering the consumption of sample and reagents. The basic CL reaction was based on the emission of CL radiation due to the reaction of luminol with hydrogen peroxide in basic medium. The CL emission has been monitored using FIAlab system. The optimum conditions and characterizations were optimized using a computer-aided simplex method. Under the optimal conditions the linear calibration graph was obtained within the range of 0.0001-1.0 μg mL-1, (r=0.9996) with detection limit of 3.3x10-5 μg mL-1 along with relative standard deviation 1.8 % (n). The flow rates were 120 μL s-1, for the aspiration into the holding coil and 80 μL s-1 for detection. The sample frequency throughput was 103 h-1. The proposed CL method was successfully applied for determination of the tested drug in pure form and its pharmaceutical formulations. The interference of some common additive compounds such as glucose, lactose, starch, talc and magnesium stearate was investigated. No interference was recorded. The obtained SIA results were statistically compared with those obtained from a reported method and did not show any significant difference.

AIM Memantine hydrochloride (Memary®), launched in June 2011 in Japan, is used in patients with moderate to severe Alzheimer's disease. We performed an integrated analysis of data obtained from different clinical studies of memantine hydrochloride conducted between 2002 and 2011 in Japan in order to examine the long-term tolerability and efficacy of this drug at a dose of 20 mg/day. METHODS Using clinical studies of memantine hydrochloride performed in Japan between 2002 and 2011, the therapeutic safety and the time course of MMSE scores in 702 subjects who had received memantine hydrochloride were examined. RESULTS The mean duration of memantine treatment was 798.1 days, with the longest duration of 3,373 days (approximately nine years and two months). The incidence of adverse events every 52 weeks of treatment ranged from 71.0% to 88.9%, and the incidence of adverse drug reactions ranged from 5.6% to 32.1%, with no associations between the incidence of adverse events and the treatment duration. There were no adverse drug reactions specific to the long-term administration of this drug. The occurrence of "adverse events" was the primary reason for drug discontinuation. During the long-term study observation period, there were many cases of adverse events and treatment discontinuation due to the background factors of the subjects, including adverse events associated with aging and progression of the underlying conditions. In addition, treatment discontinuation was also associated with admission to a nursing home or facility due to changes in home nursing care. The degree of MMSE score reduction over time was lower in the patients treated with memantine than the expected MMSE score reduction observed in the untreated patients. CONCLUSIONS Based on these findings, there are no issues regarding the tolerability of memantine hydrochloride administered at a dose of 20 mg/day over the long term. Considering changes in the MMSE score, the results indicated that memantine hydrochloride may inhibit worsening of the cognitive function for long periods of time in patients with Alzheimer's disease.

The purpose of the present work was to validate an accurate and precise high-performance liquid chromatography (HPLC) method involving ultraviolet detection for the quantitative analysis of memantine hydrochloride. In order to analyze a molecule with no chromophoric groups that could be detected by a UV/visible detector, it was necessary to extract the drug and to perform a dansylation reaction that enabled the UV/visible detection of the derivatized molecule. Separation was carried out with a 150 mm Kromasil C18 column at room temperature. The detection response, at 218 nm, was found to be linear in the concentration range from 0.5 to 50 μg/mL. The method was validated for specificity, linearity, precision, accuracy, limit of detection, limit of quantification, and robustness. The limit of detection (LOD) was 0.144 μg/mL, and the limit of quantification (LOQ) was 0.437 μg/mL. The dansylated memantine complex was stable for at least five days in all the conditions evaluated. The potential use of this method has been demonstrated by the quantification of memantine hydrochloride contained in samples from the study of itsin vitrotransdermal permeation.

Introduction: Time of flight mass spectrometry was developed and validated for quantitative determination of amantadine and memantine in drug substances and products. Materials and methods: The method was based on time of flight electron spray ionization mass spectrometry technique without preliminary chromatographic separation and made use of memantine as internal standard of amantadine, which is used as internal standard of memantine. Results and conclusion: A linear relationship between drug concentrations and peak intensity ratios of ions of the analyzed substances is established in range of 23.80-2380.00 ng mL-1 for amantadine and memantine (r=> 0.998, n=6). The method is robust and reproducible with intra-and inter-assay precision (RSD % < 2.0%). The quantification limit was 23.8 ng mL-1 for both drugs. The described method has advantages over the reported methods as the assay was completed in less than 2 min with high accuracy and selectivity.

This pilot study examined the effectiveness of memantine hydrochloride in improving cognitive functioning and behavioral symptoms in children with pervasive developmental disorders (PDDs).Subjects aged 3-12 years inclusive were enrolled in this 8-week, open-label study. Expressive and receptive language, nonverbal IQ, and nonverbal memory measures were administered at baseline and after 8 weeks of treatment with 0.4 mg/kg of memantine hydrochloride. Throughout the study, the Aberrant Behavior Checklist (ABC) was sent in weekly by parents as a measure of behavioral change.Twelve of 14 subjects completed the study. Significant improvement from baseline was noted on the memory test (Children's Memory Scale Dot Learning Subtest). There were no significant differences from baseline on measures of expressive or receptive language or nonverbal IQ. There were significant improvements on a number of ABC subscales, including hyperactivity, lethargy, and irritability. There were no overall significant statistical differences from baseline on the Clinical Global Improvement-Severity (CGI-S) scale. On the Clinical Global Improvement-Improvement (CGI-I), 4 of 14 subjects showed minimal improvement, and none was deemed "much-improved" or "very much improved."This small, prospective, open-label study suggests that memantine may be useful in the treatment of memory functioning and some behavioral symptoms in PDDs. The investigators did not see the same degree of change as endorsed by caretakers. Controlled studies are needed to substantiate and clarify these preliminary findings.

This present paper deals with the development and validation of a stability indicating high performance liquid chromatographic method for the quantitative determination of Memantine hydrochloride. Memantine hydrochloride was derivatized with 0.015 M 9-fluorenylmethyl chloroformate (FMOC) and 0.5 M borate buffer solution by keeping it at room temperature for about 20 minutes and the chromatographic separation achieved by injecting 10 μL of the derivatized mixture into a Waters HPLC system with photodiode array detector using a kromasil C18 column (150 × 4.6 mm), 5 μ, The mobile phase consisting of 80% acetonitrile and 20% phosphate buffer solution and a flow rate of 2 milliliter/minute. The Memantine was eluted at approximately 7.5 minutes. The volume of FMOC used in derivatization, concentration of FMOC and derivatization time was optimized and used. Forced degradation studies were performed on bulk sample of Memantine hydrochloride using acid (5.0 Normal (N) hydrochloric acid), base (1.0 N sodium hydroxide), oxidation (30% hydrogen peroxide), thermal (105°C), photolytic and humidity conditions. The developed LC method was validated with respect to specificity, precision (% RSD about 0.70%), linearity (linearity of range about 70-130 μg/mL), ruggedness (Overall % RSD about 0.35%), stability in analytical solution (Cumulative % RSD about 0.11% after 1450 min.) and robustness.