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donepezil + memantine ER (ADS8703 / Arimenda / ADS8704)

✓ Approved

Forest Laboratories Inc. · ACHE · Small Molecule

What is donepezil + memantine ER?

donepezil + memantine ER is a small molecule developed by Forest Laboratories Inc.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesADS8703, Arimenda, ADS8704
CompanyForest Laboratories Inc.
Drug ClassSmall Molecule
Molecular TargetACHE, GRIN1
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Forest Laboratories Inc.

Mechanism of Action

Molecular Targets

donepezil + memantine ER acts on 2 molecular targets:

ACHEacetylcholinesterase (Cartwright blood group) (N-ACHE, ACEE)
GRIN1glutamate ionotropic receptor NMDA type subunit 1 (NMD-R1, NMDA1)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

donepezil + memantine ER is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Nervous system disordersDementia Alzheimer's type✓ Approved

Related Research Articles

PubMedBMC oral health2026-09-19

Comparative in vitro evaluation of sonic, passive ultrasonic, and Er: YAG laser-activated irrigation on Enterococcus faecalis reduction and smear layer/debris removal in root canals.

Farag Rehab Ali RA, El Mekkawi Abd El Rahman O AERO, Beshr Khaled K, Sayed Mohamed M et al.

Persistent intraradicular infection remains a major cause of endodontic treatment failure because conventional syringe irrigation may not adequately reach the apical third, dentinal tubules, and canal irregularities. The aim of this in vitro study was to compare the antimicrobial efficacy and smear layer/debris removal ability of sonic activation, passive ultrasonic irrigation, and Er: YAG laser-activated irrigation using photon-induced photoacoustic streaming (PIPS), relative to conventional syringe irrigation, in prepared root canals infected with a mono-species Enterococcus faecalis biofilm. Sixty extracted single-rooted mandibular second premolars were prepared, sterilized, inoculated with E. faecalis, and randomly allocated to conventional syringe irrigation, sonic activation, passive ultrasonic irrigation, or Er: YAG/PIPS activation (n = 15). All groups received 2.5% sodium hypochlorite. Post-irrigation bacterial load was quantified as log10 CFU/mL, and smear layer/debris removal in the apical, middle, and coronal thirds was assessed by scanning electron microscopy using a five-point score. CFU values were analysed by one-way ANOVA with Tukey's post hoc test, and SEM scores by the Kruskal-Wallis test with Dunn's multiple-comparison test. Inter-examiner agreement was assessed using Cohen's kappa. Statistical significance was set at p < 0.05. Bacterial load differed significantly among groups (F(3, 56) = 85.11, p < 0.001). Mean log10 CFU/mL values were 6.41 ± 0.30 for conventional irrigation, 5.37 ± 0.26 for sonic activation, 4.12 ± 0.24 for passive ultrasonic irrigation, and 4.28 ± 0.27 for Er: YAG/PIPS activation. Passive ultrasonic and Er: YAG/PIPS activation produced significantly lower bacterial loads than sonic activation and conventional irrigation, with no significant difference between the ultrasonic and laser groups (p = 0.452). SEM scores also differed significantly (H = 38.9, p < 0.001). Overall median scores were 4.5 (IQR 4-5), 3 (IQR 3-4), and 2 (IQR 2-3) for conventional, sonic, and both ultrasonic and laser activation, respectively. All tested activation methods improved root canal disinfection and smear layer/debris removal compared with conventional syringe irrigation. Passive ultrasonic irrigation and Er: YAG/PIPS activation were more effective than sonic activation and showed comparable performance. These methods may be useful adjuncts to sodium hypochlorite irrigation, although clinical studies are needed to confirm their clinical effectiveness.

PMID 42760526
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PubMedActa neuropathologica communications2026-09-19

Neuro-glial lipid imbalance in a Drosophila model of amyotrophic lateral sclerosis 8.

Garg Lovleen L, Chaplot Kriti K, Kuppili Gowhith G, Tendulkar Shweta S et al.

Membrane Contact sites (MCS) have emerged as physiologically relevant zones that coordinate inter-organelle communication and cellular function. VAPB, an ER-resident MCS tethering protein, plays a central role in regulating MCSs through its numerous protein interactors, thereby influencing cellular homeostasis. A pathogenic missense VAPBP56S mutation causes familial Amyotrophic Lateral Sclerosis 8 (ALS8) in humans, with progressive degeneration of motor neurons. The precise mechanisms underlying the motor neurodegeneration remain poorly understood. In this study, we examine lipid imbalance in the brain of a Drosophila model of ALS8 (VAPBP58S). Specifically, we find that lipid homeostasis is disrupted in an age-dependent manner. Strikingly, cholesterol esters and sphingolipids show an age-dependent increase, while cholesterol shows a decrease. Intriguingly, from a cellular perspective, despite the accumulation of triacylglycerols (TAGs) in the brains of VAPBP58S animals, the increased neutral lipid species do not correlate with lipid droplets (LDs), which are fewer in density and smaller in size. Lipid imbalance and progressive motor dysfunction in VAPBP58S animals can be reversed by expressing VAPBWT, suggesting a relationship between VAPB activity and lipid flux. To uncover VAPB's role in lipid homeostasis, we modulate VAPB activity in neurons and glia to dissect out tissue-specific roles. We find that both cell types contribute to lipid homeostasis in differential ways. In glia, LD flux is strongly dependent on VAPB activity, a dependence further recapitulated in cultured human cell lines, suggesting evolutionary conservation of the regulatory mechanism. Thus, we hypothesize that lipid dysregulation constitutes a critical pathogenic feature of ALS8, with the VAPBP56S allele disrupting lipid homeostasis in the neuro-glial axis.

PMID 42760536
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PubMedThe Eurasian journal of medicine2026-09-19

Cinematic Rendering of Brain Magnetic Resonance Imaging: Photorealistic Visualization of Normal Neuroanatomy and Primary Brain Tumors.

Fırat Zeynep Z, Er Füsun F, Di Ieva Antonio A, Ekinci Gazanfer G et al.

Cinematic rendering (CR) is an advanced post-processing technique that generates volumetric 3-dimensional (3D) visualizations from routine clinical magnetic resonance imaging (MRI) data, potentially enhancing anatomical interpretation and spatial understanding. In this retrospective single-center study, 3.0-T MRI datasets from 35 participants (15 healthy controls and 20 patients with histopathologically confirmed primary brain tumors) were analyzed. Cinematic rendering images were generated from precontrast 3D T1-weighted magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequences. Two independent senior observers evaluated image resolution, anatomical detail, lesion depiction, visualization utility, and educational value using a 3-point Likert-type scale. Interobserver agreement was assessed using quadratic weighted Cohen's κ with bootstrap-derived 95% confidence intervals. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 29.0 (IBM Corp.; Armonk, NY, USA). Cinematic rendering provided consistent, high-fidelity 3D visualization of normal neuroanatomy and tumor-related structural alterations across different primary brain tumor histologies. Image quality ratings were uniformly high (median score: 3), with no significant differences between groups (P ≥ .229). Educational value was rated consistently by both observers across all cases. Interobserver agreement ranged from substantial to almost perfect (κ = 0.65-1.00), with perfect agreement for lesion depiction (κ = 1.00; 100% agreement). Cinematic rendering applied to routine brain MRI provides reproducible, depth-enhanced 3D visualization of normal brain anatomy and tumor-related spatial relationships. The technique demonstrates consistent image quality and interpretability across different tumor types and may serve as a supplementary tool for neuroanatomical education and spatial understanding in clinical practice. Cite this article as: Fırat Z, Er F, Ieva AD, Ekinci G, Türe U. Cinematic rendering of brain magnetic resonance imaging: photorealistic visualization of normal neuroanatomy and primary brain tumors. Eurasian J Med. 2026, 58(4), 1605, doi: 10.5152/ eurasianjmed.2026.261605.

PMID 42760764
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PubMedFrontiers in endocrinology2026-09-19

Predicting unfavorable response to initial radioactive iodine therapy in differentiated thyroid cancer: an explainable machine learning and survival analysis approach.

Gu Longxuan L, Zheng Guiwen G, Zhao Yuechao Y, Wang Jiyuan J et al.

Early post-treatment prognostic assessment may facilitate individualized follow-up in patients with differentiated thyroid cancer (DTC) after initial radioactive iodine (RAI) therapy (RAIT).This study aimed to develop and internally validate a dual-mode machine-learning framework integrating clinical information available from the pre-RAI baseline through the early post-RAI assessment period to predict subsequent unfavorable treatment response and persistence/recurrence-free survival (PRFS). A retrospective cohort of 550 DTC patients who underwent total thyroidectomy followed by initial RAIT was included. Multidimensional clinical metrics, including demographic, pathological, imaging, and serum biochemical data, were collected. Post-therapy imaging and biochemical measurements obtained at the first follow-up approximately 1-3 months after RAIT were treated as early post-RAI predictors, whereas subsequent therapeutic response was evaluated dynamically during longitudinal follow-up according to the 2025 American Thyroid Association (ATA) dynamic risk stratification framework. Patients with excellent response (ER) or indeterminate response (IndR) were classified as having a favorable response, whereas those with biochemical incomplete response (BIR) or structural incomplete response (SIR) were classified as having an unfavorable response. PRFS was defined as the interval from initial RAIT to the first subsequent documentation of BIR or SIR; patients without such an event were censored at their last follow-up. Data were randomly split into training and testing cohorts at a 7:3 ratio. Boruta and Least Absolute Shrinkage and Selection Operator (LASSO) were utilized for feature selection in binary classification, while Random Survival Forest (RSF) feature importance ranking was applied for survival modeling. We developed Decision Tree (DT), Random Forest (RF), Light Gradient Boosting Machine (LightGBM), and Multi-Layer Perceptron (MLP)-based Artificial Neural Network (ANN) models for risk classification, alongside the Cox Proportional Hazards (Cox PH) model, Gradient Boosting Survival Analysis (GBSA), RSF, and Extra Survival Trees (EST) for survival prediction. Model performance was evaluated using the Area Under the ROC Curve (AUC), Concordance Index (C-index), calibration curves, and Decision Curve Analysis (DCA). The Shapley Additive exPlanations (SHAP) framework was employed to interpret the models' decision-making mechanisms. Among 550 patients, 113 (20.5%) were classified into the unfavorable response group. The ANN classification model demonstrated superior performance on the testing cohort, with an AUC of 0.932 (95% CI: 0.888-0.967), accuracy of 0.879, specificity of 0.947, F1-score of 0.677, and the lowest Brier Score (0.091). Its clinical net benefit, as assessed by DCA, exceeded that of other models. Key predictors in the ANN risk classification model included Extrathyroidal Extension (ETE), T-stage, iodine-avid lymph node status (iodine_LN), RAI Dose, Metastatic Lymph Nodes (MLN), pre-radioiodine therapy stimulated thyroglobulin (pre_sTg), and pre-radioiodine therapy thyroglobulin antibody (pre_TgAb). Regarding PRFS prediction, the RSF model achieved the highest C-index (0.886) and a mean time-dependent AUC of 0.910 (95% CI: 0.867-0.940), outperforming other models. The core prognostic factors for the RSF model included pre_sTg, thyroglobulin at first follow-up (Tg_FU1), Pre-radioiodine Therapy Thyroglobulin/TSH Ratio (Pre_RAI_Tg_TSH_Ratio), MLN, RAI Dose, Thyroid Stimulating Hormone at first follow-up (TSH_FU1), and Thyroglobulin Antibody Reduction Rate (TgAbRR). In this single-center cohort, the ANN and RSF models demonstrated favorable internal performance for unfavorable-response classification and PRFS prediction, respectively. These findings provide preliminary proof-of-concept evidence for an early post-RAI prognostic assessment framework; however, prospective multicenter external validation is required before its generalizability or clinical utility can be established.

PMID 42760971
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PubMedAffective science2026-09-18

Prohedonic Emotion Regulation Goals in Everyday Life: How Increasing Positive Affect and Reducing Negative Affect Relate to the Emotion Regulation Process and Depression.

Tuck Alison B AB, Taillon Gigi A GA, Thompson Renee J RJ

Research finds that prohedonic emotion regulation (ER) plays a key role in psychological well-being. Despite prohedonic ER encompassing both increasing or maintaining positive affect (PA) and decreasing negative affect (NA), prohedonic ER is often examined without regard to these different forms. Research is needed to examine the frequency of these two forms of prohedonic ER and their associations with depressive symptoms to clarify their costs and benefits. In addition to investigating their frequency, we examined how they were related to perceived ER effort, difficulty, and success and whether depression moderated these associations. Participants (N = 179; M age=35.7) completed an ecological momentary assessment (EMA) protocol where they were surveyed five times a day for 14 days. At each EMA survey, participants reported their emotional responses to the most significant event since the preceding survey, their ER goals, and their ER effort, difficulty, and perceived success. Participants also completed a self-report measure of depressive symptoms. Participants more frequently reported prohedonic ER goals to decrease NA than increase or maintain PA. The ER goal of decreasing NA was associated with higher effort and difficulty (no association with perceived success). The ER goal of increasing or maintaining PA was associated with lower difficulty and higher perceived success (no association with effort). Depressive symptoms only moderated the association between maintaining/increasing PA to predict greater perceived success. These findings suggest unique benefits associated with upregulating PA compared to downregulating NA and underscore the need to differentiate prohedonic PA and NA goals in research and treatment. The online version contains supplementary material available at https://doi.org/10.1007/s42761-026-00375-8.

PMID 42756239
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PubMedAffective science2026-09-18

From Stress to Strength: Temporal Links Between Emotion Regulation, Perceived Control, and Positive Affect.

Deng Wisteria W, Chong Benjamin B, Zhu Yutong Y, Chen Mark M et al.

Emotion regulation (ER) strategies are often implemented to reduce negative affect and boost positive affect. While research has focused on the relation between negative affect and less effective ER strategy use, more work is needed to investigate how ER strategies modulate positive affect and bolster individuals' sense of agency. This EMA study examined the temporal effect of savoring on positive affect through increasing perceived controllability of daily stressors. Over a 14-day period, participants (n = 110) reported the most emotional event of the day, its level of perceived controllability, their use of 11 ER strategies (e.g., distraction, rumination), and their positive and negative affect. The use of savoring (i.e., reflect on or intensify positive experiences) emerged as both significantly relating to better affective outcomes, and, in a time-lagged mixed effects model, predicting both higher levels of self-perceived controllability and increased positive affect the day after.

PMID 42756265
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