Mitigating radiation-induced brain injury via NLRP3/NLRC4/Caspase-1 pyroptosis pathway: Efficacy of memantine and hydrogen-rich water.

Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI.

Memantine hydrochloride promotes the antibacterial effect of neutrophils against methicillin-resistant Staphylococcus aureus and the related mechanism / 中华微生物学和免疫学杂志

Objective:To investigate whether memantine hydrochloride (MEM) could promote the bactericidal effect of neutrophils against methicillin-resistant Staphylococcus aureus (MRSA) and the possible mechanism. Methods:Neutrophils were co-incubated with different concentrations of MEM and MRSA for 4 h. Then the cell lysates were collected and cultured on plate for survival bacteria counting. After co-incubation, the neutrophils were collected to detect the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). A mouse model of MRSA infection was established, and then the mice were treated with or without MEM. Blood, spleen and kidney samples were collected from the mice for bacterial colony counting and blood procalcitonin (PCT) detection. In the 48 h survival experiment, the mice were first infected with MRSA, and then treated with MEM or PBS. The survival rates of the mice were calculated and the survival curves were drawn.Results:The number of MRSA co-cultured with neutrophils decreased significantly in the presence of MEM, and within a certain concentration range, the survival number of MRSA decreased with the increase of MEM concentration. Moreover, MEM could significantly promote the production of ROS by neutrophils and the formation of NETs. In vivo experiment showed that the concentration of PCT in mouse blood samples was lower in the MRSA+ MEM group than in the MRSA+ PBS group. The animal experiment also revealed that MEM significantly decreased the bacteria loads in mouse blood and organs and increased the 48 h survival rate after MRSA infection.Conclusions:MEM could significantly promote the bactericidal effect of neutrophils against MRSA, which might be related to the enhanced generation of ROS by neutrophils and the formation of NETs.

Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions.

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-1ß, and TNF-α in the mice brain. Western blotting was used to assess the expression of ß-secretase (BACE1), amyloid precursor protein (APP), APPß, 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 Aß plaque accumulation by inhibiting BACE1 and APP expression (P < 0.05 or P < 0.001). Besides, the combination group markedly inhibited the levels of IL-1ß, IL-6, and TNF-α in hippocampus (P < 0.001), as well as activities of SOD, CAT, and GSH-Px in serum (P < 0.001). By contrast, the combination group improved synaptic plasticity by enhancing SYN, PSD95, and GAP43 expression. 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 Aß deposition, neuroinflammation, oxidative damage, and improving synaptic plasticity.

Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?

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. 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?

[The use of Akatinol Memantine in the treatment of gait disturbances in Parkinson's disease]. / Vliyanie Akatinola Memantina na narusheniya khod'by na razvernutykh stadiyakh bolezni Parkinsona.

OBJECTIVE: To assess the efficacy of memantine hydrochloride in the treatment of GD in PD patients. MATERIALS AND METHODS: Patients of the main group (n=30) received memantine hydrochloride (akatinol memantine) in a dose of 20 mg/day for 3 months in addition to antiparkinsonian therapy. Patients of the comparison group (n=25) received only antiparkinsonian drugs. Cognitive rating scales and computerized gait assessment protocol were performed in both groups twice in 3 months interval in order to examine cognitive deficit and gait parameters. RESULTS: The increase in MMSE scores, improvement in gait cycle phases ratio and increase of cadence according to computerized gait analysis were observed in the main group compared to the comparison group. CONCLUSION: The improvement in gait achieved during the study confirms that the treatment of cortical gait disturbances in patients with PD using memantine hydrochloride is a promising area of therapy.

A rapid FTIR spectroscopic assay for quantitative determination of Memantine hydrochloride and Amisulpride in human plasma and pharmaceutical formulations.

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 ß-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.

A new spectrofluorimetric assay for quantification of Amisulpride and Memantine hydrochloride in real human plasma sample and pharmaceutical formulations via Hantzsch reaction.

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.

Utility of chromogenic property of 2, 2-dihydroxyindane-1, 3-dione for quantification of Memantine hydrochloride in pure, pharmaceutical preparation and application to uniformity testing.

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.

Therapeutic effect of rosuvastatin combined with memantine hydrochloride on vascular dementia / 中国基层医药

Objective@#To investigate the efficacy and safety of rosuvastatin combined with memantine hydrochloride in the treatment of vascular dementia.@*Methods@#Sixty-six patients with vascular dementia admitted to the Hospital of Zhejiang Provincial Armed Police Force and Haining Kanghua Hospital from January 2016 to January 2018 were enrolled.According to the digital table, the patients were divided into the observation group and the control group, with 33 cases in each group.Both two groups were given routine treatment.The control group was treated with rosuvastatin, and the observation group was given rosuvastatin combined with memantine hydrochloride.Both two groups were treated for 12 weeks.The ADL score and MoCA score, oxidative stress index, inflammatory factor, cerebral kinetic index changes, clinical efficacy and adverse reactions after treatment were compared between the two groups.@*Results@#The therapeutic effect of the observation group was 87.88%(29/33), which was significantly higher than 63.64%(21/33) of the control group (χ2=5.280, P=0.022). After treatment, the ADL, MoCA, SOD levels, Vmax and BHI of the observation group were (41.26±5.37)points , (24.23±1.71)points, (112.27±15.35)μU/L, (65.15±11.75)cm/s, (0.79±0.36), respectively, which were higher than those of the control group [(36.19±4.07)points, (20.25±1.46)points, (93.84±12.76)μU/L, (59.15±11.74)cm/s, (0.58±0.26)], the differences were statistically significant (t=4.322, 10.168, 5.304, 2.075, 2.846, all P<0.05). The levels of MDA, HCy, TNF-α, IL-6 and IL-1β in the observation group were (6.37±1.05)μmol/L, (31.36±9.59)μmol/L, (184.15±15.12)ng/L, (229.85±27.69)ng/L, (127.64±17.86)ng/L, respectively, which were lower than those in the control group [(7.32±1.07)μmol/L, (42.27±11.34)μmol/L, (208.72±15.26)ng/L, (262.75±25.64)ng/L, (148.75±18.64)ng/L], the differences were statistically significant (t=3.640, 4.220, 6.570, 5.008, 4.698, all P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05).@*Conclusion@#The clinical efficacy of rosuvastatin combined with memantine hydrochloride in the treatment of patients with vascular dementia can significantly reduce oxidative stress and inflammatory response, improve cerebral hemodynamics and cognitive function, and improve patients’ quality of life.

Therapeutic effect of rosuvastatin combined with memantine hydrochloride on vascular dementia / 中国基层医药

Objective To investigate the efficacy and safety of rosuvastatin combined with memantine hydrochloride in the treatment of vascular dementia.Methods Sixty-six patients with vascular dementia admitted to the Hospital of Zhejiang Provincial Armed Police Force and Haining Kanghua Hospital from January 2016 to January 2018 were enrolled.According to the digital table,the patients were divided into the observation group and the control group,with 33 cases in each group.Both two groups were given routine treatment.The control group was treated with rosuvastatin,and the observation group was given rosuvastatin combined with memantine hydrochloride.Both two groups were treated for 12 weeks.The ADL score and MoCA score,oxidative stress index,inflammatory factor,cerebral kinetic index changes,clinical efficacy and adverse reactions after treatment were compared between the two groups.Results The therapeutic effect of the observation group was 87.88％ (29/33),which was significantly higher than 63.64％ (21/33) of the control group (x2 =5.280,P =0.022).After treatment,the ADL,MoCA,SOD levels,Vmax and BHI of the observation group were (41.26 ± 5.37) points,(24.23 ± 1.71) points,(112.27 ± 15.35) μU/L,(65.15 ± 11.75) cm/s,(0.79 ± 0.36),respectively,which were higher than those of the control group [(36.19 ± 4.07) points,(20.25 ± 1.46) points,(93.84 ± 12.76) μU/L,(59.15 ± 11.74) cm/s,(0.58 ± 0.26)],the differences were statistically significant (t =4.322,10.168,5.304,2.075,2.846,all P ＜ 0.05).The levels of MDA,HCy,TNF-α,IL-6 and IL-1β in the observation group were (6.37 ± 1.05) μmol/L,(31.36 ± 9.59) μmol/L,(184.15 ± 15.12) ng/L,(229.85 ± 27.69) ng/L,(127.64 ± 17.86) ng/L,respectively,which were lower than those in the control group [(7.32 ± 1.07) μmol/L,(42.27 ± 11.34) μmol/L,(208.72 ± 15.26) ng/L,(262.75 ± 25.64) ng/L,(148.75 ± 18.64) ng/L],the differences were statistically significant (t =3.640,4.220,6.570,5.008,4.698,all P ＜ 0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusion The clinical efficacy of rosuvastatin combined with memantine hydrochloride in the treatment of patients with vascular dementia can significantly reduce oxidative stress and inflammatory response,improve cerebral hemodynamics and cognitive function,and improve patients' quality of life.

[Modern views on gait impairment in Parkinson`s disease and its correction]. / Sovremennye predstavleniia o narusheniiakh khod'by pri bolezni Parkinsona i metodakh ikh korrektsii.

The article reviews the causes of gait impairment in patients with Parkinson's disease (PD). The emphasis is made on modern ideas, according to which gait impairment in PD is caused by a multisystem lesion and non-dopaminergic dependent mechanisms play the leading role. It is highlighted that gait impairment in PD is associated with the disruption of frontal/subcortical neural pathways which requires a special approach to pharmacological and non-pharmacological therapy. Based on pathogenetic mechanisms, much attention is paid to anti-dementia medications. Attention is drawn to the fact that the use of memantine hydrochloride (akatinol memantine) is a promising direction for gait impairment correction in the advanced and late stages of PD due to the improvement of glutamatergic transfer from the striatum to the specific areas of the cerebral cortex involved in gait control. The results of the latest clinical trials are analyzed.

Effects of Memantine Hydrochloride on Cognitive Function, Cerebral Hemodynamics and Oxidative Stress Level in Patients with Vascular Dementia / 中国药房

OBJECTIVE: To investigate the effects of memantine hydrochloride on cognitive function, cerebral hemodynamics and oxidative stress level in patients with vascular dementia (VD). METHODS: A total of 70 VD patients in the Third Affiliated Hospital of Xinxiang Medical College from Feb. 2013 to Feb. 2015 were divided into control group (36 cases) and observation group (34 cases) aoccording to random number table. Observation group was given Memantine hydrochloride tablets orally with initial dose of 5 mg/d, qd, increasing by 5 mg/week gradually, maintaining at 20 mg/d, qd, at 4th week. Control group was given Piracetam tablets 0. 8 g orally, tid. A treatment course of 2 groups lasted for 4 weeks, and both were treated for 6 courses. Clinical efficacies as well as MoCA scores, ADL scores, systolic peak velocity (Vmax),diastolic peak velocity (Vmin),pulsatility index (PI), resistance index (RI) and breath holding index (BHI) of middle cerebral artery, the levels of MDA, SOD and Hcy were observed in 2 groups. The occurrence of ADR was recorded. RESULTS: Four, two patients withdrew from the study in control and observation group, respectively, and 32 patients in each group completed the study. The total response rate of observation group was 87. 50％, which was significantly higher than 65. 63％ of control group, with statistical significance (P＜0. 05). Before treatment, there was no statistical significance in above indexes between 2 groups (P＞0. 05). After treatment, MoCA, ADL scores and SOD levels of 2 groups were increased significantly, while MDA and Hcy levels were decreased significantly; Vmax and BHI of observation group were increased significantly, and above indexes of observation group was significantly better than those of control group, with statistical significance (P＜0. 05). There was no statistical significance in Vmin, PI or RI between 2 groups before and after treatment, and Vmax or BHI of control group before and after treatment (P＞0. 05). ADRs of 2 groups were mild, and there was no statistical significance in the incidence of ADR between 2 groups (P＞0. 05). CONCLUSIONS: Memantine hydrochloride in the treatment of VD patients can improve the cerebral hemodynamics, reduce oxidative stress and improve cognitive function with good safety.

Memantine-derived drugs as potential antitumor agents for the treatment of glioblastoma.

Glioblastoma is one of the most aggressive malignant primary brain cancer in adults. To date, surgery, radiotherapy and current pharmacological treatments are not sufficient to manage this pathology that has a high mortality rate (median survival 12-15months). Recently, anticancer multi-targeted compounds have attracted much attention with the aim to obtain new drugs able to hit different biological targets that are involved in the onset and progression of the disease. Here, we report the synthesis of novel memantine-derived drugs (MP1-10) and their potential antitumor activities in human U87MG glioblastoma cell line. MP1-10 were synthetized joining memantine, which is a NMDA antagonist, to different histone deacetylase inhibitors to obtain one molecule with improved therapeutic efficacy. Biological results indicated that MP1 and MP2 possessed more potent anti-proliferative effects on U87MG cells than MP3-10 in a dose-dependent manner. MP1 and MP2 induced significant cell death by apoptosis characterized by apoptotic morphological changes in Hoechst staining. Both drugs also exhibited non-genotoxic and only mild cytotoxic effects in human whole blood cells. However, only MP1, showing good chemico-physical properties (solubility, LogP) and enzymatic stabilities in gastric and intestinal fluids, can be considered a suitable candidate for in vivo pharmacokinetic studies.

Post-injury administration of a combination of memantine and 17ß-estradiol is protective in a rat model of traumatic brain injury.

Traumatic brain injury (TBI) often leads to substantial adverse cognitive and health outcomes, including permanent disability and death. Preventing these outcomes requires attenuation of the secondary biochemical damage that follows the initial biomechanical insult, but a clinically proven pharmacotherapeutic capable of such has not been identified. In fact, the heterogeneous nature of TBI and the complexity of secondary injury cascades suggest a polytherapeutic approach that targets multiple pathways might be necessary. We and others have reported that 17ß-estradiol (E2) is neuroprotective in models of central nervous system injury. Although E2 is neuroprotective and favorably modulates several key components of secondary injury, it does not effectively block the destructive excitotoxic cascade. Thus, administering E2 in combination with a second drug that targets excitotoxicity, such as the FDA-approved uncompetitive NMDA receptor antagonist memantine hydrochloride, may provide additional benefits. Here, we assessed the neuroprotective potential of an acutely administered intravenous bolus dose of a combination of memantine and E2 after induction of experimental TBI in the clinically relevant lateral fluid percussion model. Our results indicate that the combination of these drugs conferred neuroprotection by increasing neuronal survival and decreasing neuronal degeneration in the hippocampus and cortex ipsilateral to injury. Furthermore, administration of this combination improved vestibulomotor deficits and modestly reduced anxiety. We conclude that further investigation of the neuroprotective potential of memantine administered with E2 is warranted.

Clinical Observation of Memantine Hydrochloride Tablets Combined with Tianzhi Granules in the Treat-ment of Vascular Dementia / 中国药房

OBJECTIVE:To investigate the clinical efficacy and safety of Memantine hydrochloride tablets combined with Tianzhi granules in the treatment of vascular dementia. METHODS:A total of 94 patients with vascular dementia selected from our hospital during Jun. 2014-Jun. 2016 were divided into observation group and control group according to random number table,with 47 cases each. Besides basic therapy,control group was given Tianzhi granules 5 g,po,tid. Observation group was additionally given Memantine hydrochloride tablets with initial dose of 5 mg,increasing by 5 mg every week,maintaining dose of 20 mg/d at 4th week,po,qd,on the basis of control group. Both groups received treatment for consecutive 4 weeks. Clinical efficacies as well as MMSE,MoCA,ADL scores,the levels of brain-derived neurotrophic factor(BDNF),malondialdehyde(MDA)and super-oxide dismutase(SOD)before and after treatment were observed in 2 groups.The occurrence of ADR was recorded.RESULTS:To-tal response rate of observation group(80.85%)was significantly higher than control group(61.70%),with statistical significance (P<0.05). Before treatment,there was no statistical significance in MMSE,MoCA,ADL scores,the levels of BDNF,MDA or SOD between 2 groups(P>0.05).After treatment,MMSE,MoCA,ADL scores,the levels of BDNF and SOD in 2 groups were increased significantly,while MDA level was decreased significantly;observation group was significantly better than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Memantine hydrochlo-ride tablets combined with Tianzhi granules in the treatment of vascular dementia show significant therapeutic efficacy,and can im-prove cognitive function,daily living activity and BDNF,MDA and SOD levels of patients with good safety.

Clinical Observation of Memantine Hydrochloride Tablets Combined with Tianzhi Granules in the Treat-ment of Vascular Dementia / 中国药房

OBJECTIVE:To investigate the clinical efficacy and safety of Memantine hydrochloride tablets combined with Tianzhi granules in the treatment of vascular dementia. METHODS:A total of 94 patients with vascular dementia selected from our hospital during Jun. 2014-Jun. 2016 were divided into observation group and control group according to random number table,with 47 cases each. Besides basic therapy,control group was given Tianzhi granules 5 g,po,tid. Observation group was additionally given Memantine hydrochloride tablets with initial dose of 5 mg,increasing by 5 mg every week,maintaining dose of 20 mg/d at 4th week,po,qd,on the basis of control group. Both groups received treatment for consecutive 4 weeks. Clinical efficacies as well as MMSE,MoCA,ADL scores,the levels of brain-derived neurotrophic factor(BDNF),malondialdehyde(MDA)and super-oxide dismutase(SOD)before and after treatment were observed in 2 groups.The occurrence of ADR was recorded.RESULTS:To-tal response rate of observation group(80.85%)was significantly higher than control group(61.70%),with statistical significance (P<0.05). Before treatment,there was no statistical significance in MMSE,MoCA,ADL scores,the levels of BDNF,MDA or SOD between 2 groups(P>0.05).After treatment,MMSE,MoCA,ADL scores,the levels of BDNF and SOD in 2 groups were increased significantly,while MDA level was decreased significantly;observation group was significantly better than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Memantine hydrochlo-ride tablets combined with Tianzhi granules in the treatment of vascular dementia show significant therapeutic efficacy,and can im-prove cognitive function,daily living activity and BDNF,MDA and SOD levels of patients with good safety.

Formula Optimization of Memantine Hydrochloride Sustained Release Pellets by Box-Behnken Surface Response Design / 中国药师

Objective: To optimize the formula of memantine hydrochloride sustained release pellets and investigate the drug release in vitro.Methods: Memantine hydrochloride sustained release pellets were prepared by a fluidized bed.The factors such as inlet air temperature, spray pressure and feeding rate were optimized by orthogonal tests.The Box-Behnken response surface methodology was used to screen the major influencing factors (ethyl cellulose aqueous dispersion, PEG 6000 and the coating weight) in the release of memantine hydrochloride.The coating formula and coating weight were optimized with the cumulative release rate of memantine hydrochloride in 2, 6,and 12 h as the response values.The drug release in vitro was also studied.Results: The optimum preparation parameters of the pellets were as follows: the inlet air temperature of 45℃, the spray pressure of 1.0 bar, and the feeding rate of 1.5 r·min-1.The best sustained release coating formula was as follows: the content of ethyl cellulose aqueous dispersion of 8.4%, the content of PEG 6000 of 2.3%, and the weight gain of sustained release layer of 16.7%.The memantine hydrochloride sustained release pellets had notable sustained release effect.Conclusion: Orthogonal tests and Box-Behnken response surface method can be used for the formula optimization of memantine hydrochloride sustained-release pellets.The established fitting model is simple with good predictability.

Determination of Content and Content Uniformity of Memantine Hydrochloride Dispersible Tablets by an Internal Standard Method of GC / 中国药师

Objective: To establish a GC method for the determination of content and content uniformity of memantine hydrochloride dispersible tablets.Methods: The sample was dissolved in water, alkalified by sodium hydroxide solution and extracted by methylene chloride.An HP-5 gas chromatography column (50 m×0.32 mm, 1.05 μm) was used.The column temperature was programming increased, and the initial temperature maintained at 120 ℃ for 3 min, and then raised to 220 ℃ at a rate of 10℃·min-1 and maintained for 7 min.A hydrogen flame ionization detector (FID) was used and the split ratio was 1∶1.The inlet temperature was 230 ℃ and the detector temperature was 260 ℃.The injection volume was 1 μl and the carrier gas was nitrogen with high purity at a flow rate of 3.0 ml·min-1.Adamantane was used as the internal standard, and the internal standard method was used for the calculation.Results: The calibration curve was linear over the range of 0.05-1.0 mg·ml -1 (r=0.999 7).The detection limit and the limit of quantification was 1.1 ng and 3.3 ng, respectively.The average recovery was 100.2% (RSD =0.73%, n=9).Conclusion: The method has the advantages of simple operation, small extraction process toxicity, little environmental pollution, high accuracy and high specificity, and can be used for the determination of content and content uniformity of memantine hydrochloride dispersible tablets.

Memantine alters striatal plasticity inducing a shift of synaptic responses toward long-term depression.

Memantine is an open channel blocker that antagonizes NMDA receptors reducing the inappropriate calcium (Ca(2+)) influx occurring in presence of moderately increased glutamate levels. At the same time, memantine has the ability to preserve the transient physiological activation of NMDA receptor, essential for learning and memory formation at synaptic level. In the present study we investigated the effects exerted by memantine on striatal synaptic plasticity in rat striatal spiny projection neurons (SPNs). In vitro application of memantine in striatal slices elicited a disruption of long-term potentiation (LTP) induction and maintenance, and revealed, in the majority of the recorded neurons, a long-term depression (LTD), whose amplitude was concentration-dependent (0.3-10 µM). Interestingly, preincubation with the dopamine (DA) D2 receptor antagonist sulpiride (10 µM) prevented memantine-induced LTD and restored LTP. Moreover, the DA D2 agonist quinpirole (10 µM), similarly to memantine, induced LTD in a subgroup of SPNs. In addition, memantine-induced LTD was also prevented by the CB1 endocannabinoid receptor antagonist AM 251 (1 µM). These results suggest that the actions exerted by memantine on striatal synaptic plasticity, and in particular the induction of LTD observed in SPNs, could be attributed to its ability to activate DA D2 receptors. By contrast, blockade of NMDA receptor is not involved in memantine-induced LTD since APV (30 µM) and MK801 (10 µM), two NMDA receptor antagonists, failed to induce this form of synaptic plasticity. Our data indicate that memantine could be used as treatment of neurological disorders in which DA D2 receptor represents a possible therapeutic target.

A new simultaneous derivatization and microextration method for the determination of memantine hydrochloride in human plasma.

A simple and sensitive method for simultaneous derivatization and hollow fiber liquid phase microextraction (HF-LPME) followed by high performance liquid chromatography-fluorescence detection (HPLC-FL) to determine memantine hydrochloride (MT) in human plasma was developed. The derivatization and microextraction was combined to a single step to ensure the precision. What is more, the derivatization reaction accelerated the mass transfer during the process of microextraction. The hollow fiber was filled with cyclohexane and dansyl chloride (derivatization agent) as acceptor phase and submersed in the alkalinized plasma sample. The system was submitted to stirring at 800rpm for 50min at 40°C. Different experimental parameters were systematically evaluated by response surface methodology. Under the optimized conditions, the calibration curve was linear in the range of 1-100ng/mL (r=0.9991) with a limit of detection of 0.1ng/mL (S/N=3). The precision estimated as the relative standard deviation (RSD) was less than 4.5% and the accuracy was 94.3-100.7%. The present method was successfully applied to determine MT in human plasma samples.