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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

PubMedCommunications biology2026-09-20

Beyond ER-Golgi trafficking: unconventional protein secretion as a new design frontier for synthetic secretion switches in mammalian cells.

Shi Bingshun B, Qiu Xinyuan X, Jiang Yongheng Y, Cai Jiabo J et al.

Mammalian gene switches enable programmable cell behavior. However, current switches on transcriptional and translational layers require de novo RNA and protein synthesis, and secreted outputs must additionally undergo folding, post-translational processing, and intracellular trafficking, imposing delays that limit rapid extracellular responses. Rapid secretion-control switches instead act on pre-synthesized proteins by controlling retention, trafficking, storage, or release. Most current platforms exploit the classical endoplasmic reticulum (ER)-Golgi pathway, including engineered stimulus-secretion coupling in specialized secretory cells and ER retention, retrieval-signal cleavage, or synchronized trafficking in general mammalian hosts. Although these strategies improve response kinetics, they remain limited by ER dependence, host-cell specificity, cargo compatibility, basal leakage, and post-release transport delays. Here, we review current secretion-control architectures and highlight unconventional protein secretion as an underexplored source of design principles for positioning regulatory control closer to terminal protein export and expanding the architectures available for mammalian secretion control.

PMID 42763312
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PubMedCureus2026-09-20

Histomorphological and Immunohistochemical Profile of Malignant Breast Lesions in a Tertiary Care Center of Central India: A Cross-Sectional Study.

Himani Himani H, Jain Atul A, Agarwal Shikha S, Gangwani Amar A

Breast carcinoma is a heterogeneous malignancy with variable histomorphological patterns and immunohistochemical profiles. Evaluation of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) expression provides important prognostic and predictive information for treatment planning. Ki-67 was not evaluated in the present study; therefore, the reported immunohistochemical subgroups were based only on ER, PR, and HER2/neu expression. This study aimed to assess the histomorphological and immunohistochemical profile of malignant breast lesions in a tertiary care center in Central India. This cross-sectional observational study included 84 patients with histopathologically confirmed malignant breast lesions. Tumors were classified according to standard histopathological criteria and graded using the Nottingham modification of the Bloom-Richardson system. Immunohistochemistry was performed for ER, PR, and HER2/neu. Molecular subtypes were assigned based on ER, PR, and HER2/neu expression. The most common age group was 41-50 years (n = 39, 46.4%). Invasive ductal carcinoma, not otherwise specified, accounted for 95.2% (80/84) of cases. Grade III tumors were observed in 58.3% (49/84), and lymph node metastasis was present in 58.3% (49/84). ER, PR, and HER2/neu positivity were observed in 59.5%, 53.6%, and 29.8% of cases, respectively. The hormone receptor (HR)-positive/HER2-negative subgroup was the most common (59.5%), followed by HR-positive/HER2-positive (17.9%), HR-negative/HER2-positive (11.9%), and triple-negative (10.7%) subgroups. On descriptive analysis, HR positivity decreased with increasing tumor grade and nodal positivity, whereas HER2/neu positivity increased. Histopathological evaluation combined with ER, PR, and HER2/neu immunohistochemistry provides important information for tumor classification, prognostic assessment, and therapeutic decision-making in breast carcinoma. Routine integrated reporting is essential for individualized management of malignant breast lesions.

PMID 42763585
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PubMedBritish journal of cancer2026-09-20

Inflammatory biomarkers and risk of postmenopausal oestrogen receptor-positive breast cancer: a case-cohort analysis.

Albers Frances Em FE, Swain Christopher Tv CT, Dashti S Ghazaleh SG, Rinaldi Sabina S et al.

The role of systemic inflammation in postmenopausal breast carcinogenesis remains unclear. Using a case-cohort study within the Melbourne Collaborative Cohort Study, we estimated the effects of circulating inflammatory biomarkers on the risk of postmenopausal oestrogen receptor (ER)-positive breast cancer. We included 1223 females (347 cases) who were postmenopausal at blood collection. For each biomarker, risk ratios (RRs) and 95% confidence intervals (CIs) for ER-positive breast cancer were estimated (1) per-doubling in biomarker concentration and (2) for quartiles of concentration with the lowest category as the reference, using weighted Poisson regression with a robust variance estimator. The risk of postmenopausal ER-positive breast cancer increased per doubling in blood concentrations of leptin (RR: 1.13, 95% CI: 1.03, 1.25), adiponectin (RR: 1.10, 95% CI: 0.90, 1.34), tumour necrosis factor-alpha (RR: 1.27, 95% CI: 0.96, 1.68), and interleukin-10 (RR: 1.14, 95% CI: 1.01, 1.29). The RR for a doubling of the leptin-to-adiponectin ratio was 1.07 (0.99, 1.16). RRs for other biomarkers were 1.04 (0.93, 1.17) for interferon-gamma, 1.01 (0.88, 1.17) for interleukin-6, 0.98 (0.83, 1.16) for interleukin-8, and 1.03 (0.95, 1.11) for C-reactive protein. Systemic inflammation may be important in the risk of developing ER-positive breast cancer for postmenopausal females.

PMID 42763311
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PubMedCureus2026-09-20

A Greek Real-World Experience With the Implementation of the EndoPredict Gene Signature in a Cohort of Pre-menopausal and Post-menopausal Patients With ER+/HER2- Breast Cancer.

Pantazidis George G, Sourla Antigoni A, Vasiageorgi Aggeliki A, Yfanti Christina C et al.

Background EndoPredict® is a guideline-recommended gene signature assay guiding whether adjuvant treatment should include chemotherapy or not. The EndoPredict® Clinical (EPclin) Risk Score combines molecular and clinical data to predict the distant recurrence of breast cancer, providing valuable information about the prognosis and chemotherapy benefit in both pre- and post-menopausal patients. Methodology This is a real-world, retrospective study aiming to characterize the EPclin Risk Score's utility in 200 consecutively selected Greek patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer, enrolled in a single institution, considering their clinicopathological features and menopausal status, with emphasis on its role in identifying patients suitable for treatment de-escalation. Results In this study, 100 pre-menopausal and 100 post-menopausal ER+/HER2- breast cancer patients were included. Among the pre-menopausal subgroup, 65% of the patients were classified as low risk and the other 35% as high risk, while among the post-menopausal subgroup, the low-risk and high-risk patients were 66% and 34%, respectively. A notable 30% of node-positive premenopausal patients were characterized by EPclin as at a low risk of breast cancer. Conclusions The EPclin Risk score has the ability to stratify and guide therapy decisions in ER+/HER2- breast cancer patients. It classifies the recurrence risk differently from traditional assessments and identifies low-risk premenopausal patients with node-positive disease. This may provide a de-escalation treatment pathway for such patients but requires further clinical validation.

PMID 42763779
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PubMedJournal of public health (Oxford, England)2026-09-20

Individualized breast cancer survival prediction in clinical practice: a SEER-derived interactive web tool integrating molecular and anatomical factors.

Kumar Mukesh M, Sm-Rahman Atiqur A, Bhattacharjee Atanu A

Accurate patient-level risk prediction supports treatment decisions in breast cancer. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) registry, we developed and internally validated an interactive web-based survival calculator integrating molecular and anatomical predictors. We analysed 1 742 998 women diagnosed with breast cancer in SEER between 2010 and 2020, when human epidermal growth factor receptor 2 (HER2) ascertainment was reliable. Predictors included age at diagnosis, HER2, oestrogen/progesterone receptor (ER/PR) status, and American Joint Committee on Cancer (AJCC) 6th-edition tumour, node, metastasis (TNM) staging. HER2 was recoded to separate equivocal from unknown/untested cases. A multivariable Cox model was fitted and assessed on a held-out 30% sample using discrimination and calibration. Robustness was evaluated using stratified Cox, Royston-Parmar flexible parametric, and restricted mean survival time (RMST) analyses. Discrimination was good (Harrell C-index 0.72; time-dependent area under the time-dependent receiver operating characteristic (ROC) curve 0.76-0.78 at 12-120 months) with close calibration. Older age, distant metastasis, advanced T stage, nodal involvement, and ER/PR-negative status independently increased mortality. HER2-positive disease showed lower risk, whereas equivocal and unknown HER2 had higher risk. Findings remained stable across sensitivity analyses; RMST showed ~ 61 fewer restricted-mean survival months for M1 disease. The tool provides individualized survival probabilities from routine clinical and molecular inputs. It is prognostic, not predictive, and should complement rather than replace clinical judgement alone.

PMID 42763803
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PubMedCureus2026-09-20

Myoepithelioma-Like Tumor of the Vulvar Region Presenting as a Painful Vulvar Nodule in a Young Woman: A Case Report.

Yoshida Mitsuaki M, Nguyen Thao T TT, Iwata Takahiro T, Shimasaki Miyako M et al.

Myoepithelioma-like tumor of the vulvar region (MELTVR) is a rare mesenchymal subcutaneous tumor of low malignant potential that occurs in adult women and has typical histological features, including loss of SMARCB1 (INI1) expression. This report describes the case of a 23-year-old woman with a painful vulvar subcutaneous nodule and a diagnosis of MELTVR and describes the challenges in the approach to definitive diagnosis. A 23-year-old woman presented with a three-month history of right pubic pain. Imaging revealed a 25-mm inguinal lesion without metastasis. Biopsy demonstrated spindle and plasmacytoid tumor cells in myxoid and hypercellular areas, suggesting myoepithelioma. Although necrosis and mitotic activity were not evaluable in the biopsy specimen, malignant potential could not be excluded. Complete surgical excision was subsequently performed. The resected tumor measured 45 × 35 × 15 mm and showed multilocular solid and gelatinous areas. Histologically, lobulated growth, marked atypia, necrosis, and mitotic activity (9/10 HPF) were identified. Immunohistochemically, tumor cells showed positivity for estrogen receptor (ER) and progesterone receptor (PgR), along with loss of SMARCB1 (INI1) expression. Other markers, such as neural and myoepithelial markers, were negative. Fluorescence in situ hybridization (FISH) analysis showed no Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement. MELTVR was diagnosed based on integrated clinicopathological and molecular findings. Biopsy specimens may fail to capture key diagnostic features of MELTVR because of intratumoral heterogeneity. Definitive diagnosis requires comprehensive evaluation of resection specimens with immunohistochemical and molecular analyses. This case may contribute to establishing diagnostic criteria for this rare entity.

PMID 42763470
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