rivastigmine / Generic mfg. - LARVOL DELTA

Isatin derivatives as potent cholinesterase inhibitors: recent developments and future challenges. (PubMed, RSC Adv) - "However, the currently approved small molecules, including tacrine, donepezil, rivastigmine, and galantamine, are limited by their modest efficacy, poor selectivity, and adverse effects, necessitating the development of improved therapeutic agents. Structure-activity relationship studies have revealed the critical influence of electronic effects, linker optimization, N-substitution, and molecular hybridization on inhibitory potency and selectivity. This review summarizes the most promising isatin-based cholinesterase inhibitors reported from 2020 to the present, highlighting their biological activities, structure-activity relationships, and potential for the development of next-generation anti-Alzheimer therapeutics."

Journal • Review • Alzheimer's Disease • CNS Disorders • Pain

Computational discovery and dynamic profiling of dual acetylcholinesterase and monoacylglycerol lipase inhibitors for Alzheimer's disease. (PubMed, Mol Divers) - "This study employed an integrative in silico workflow to identify potential dual acetylcholinesterase/monoacylglycerol lipase inhibitors from a molecular library derived from known inhibitors (rivastigmine, JZL-184, ABX-1431). Additionally, H34 displayed favorable pharmacokinetic properties and low predicted acute toxicity. These results highlight H34 as a promising dual-target candidate for Alzheimer's disease therapy and illustrate the effectiveness of integrated computational strategies in early-stage drug discovery."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Evaluation of the effects of alpha-lipoic acid on cyclosporine-induced memory dysfunction and cellular immunosuppression in rats. (PubMed, Phytomedicine) - "These findings suggest that ALA may exert neuroprotective effects against CsA-induced memory dysfunction while preserving the inhibitory effects of CsA on lymphocytes."

Journal • Preclinical • CNS Disorders • Immunology • BDNF • IFNG

Neuromodulation to Promote Recovery Following Traumatic Brain Injury: A Narrative Review of Current Pharmacologic and Non-Pharmacologic Approaches. (PubMed, Brain Sci) - "This narrative review summarizes current evidence supporting pharmacologic neuromodulatory therapies, including central nervous system stimulants (methylphenidate and modafinil), dopaminergic agents (amantadine and bromocriptine), acetylcholinesterase inhibitors (donepezil and rivastigmine), and selective serotonin reuptake inhibitors (sertraline and fluoxetine). However, current evidence is limited by heterogeneous study populations, small sample sizes, inconsistent outcome measures, and a paucity of long-term randomized controlled trials. Future research should prioritize adequately powered comparative studies, standardized outcome measures, biomarker-guided patient selection, and multimodal treatment strategies to optimize neurological recovery following TBI."

Journal • Review • CNS Disorders • Fatigue • Vascular Neurology

Biomarkers, Diagnostics, and Emerging Therapies in Alzheimer's Disease: A Comprehensive Systematic Review (2015-2025). (PubMed, Cent Nerv Syst Agents Med Chem) - "This review highlights the critical need for future AD research to bridge identified gaps in early detection, focus on improving early diagnosis, developing more effective treatments, refining existing drugs and therapies, and understanding the underlying disease progression mechanisms."

Biomarker • IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Gene Therapies • Infectious Disease • Vascular Neurology

Pharmacological interventions targeting cognition and related clinical outcomes in vascular dementia: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Eur J Clin Pharmacol) - "Galantamine and memantine showed small short-term cognitive effects; EGb 761® suggested a fragile, very low-certainty signal; patient-important benefits remain uncertain."

Clinical • Clinical data • Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia

Safety Comparison of Acetylcholinesterase Inhibitors Using FAERS Spontaneous-Reporting Data: Drug-Specific Reporting Signals and Time-to-Onset Dynamics. (PubMed, Curr Alzheimer Res) - "Donepezil, galantamine, and rivastigmine showed distinct FAERS reporting profiles and early post-initiation TTO patterns. These findings are hypothesis-generating and require confirmation in independent pharmacovigilance or clinical datasets."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dermatology • Pruritus

Pharmacological treatments of REM sleep behaviour disorder in synucleinopathies: a systematic review of effectiveness and safety. (PubMed, Sleep Med) - "pharmacological treatment of synucleinopathy-associated RBD remains supported by limited and heterogeneous evidence. Larger randomised trials using standardised clinical and vPSG outcomes are needed to clarify efficacy and safety."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Psychiatry • Sleep Disorder

Cholinesterase inhibitors and sexual disinhibition in dementia: a FAERS disproportionality study. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Sexual disinhibition under cholinesterase inhibitors (CHEIs; donepezil, rivastigmine, galantamine) appears only as scattered case reports and is largely absent from product labels. The sexual disinhibition signal was reproducible and consistent across all three CHEIs relative to memantine, stronger than for other impulse/reward behaviours and largely absent from current labels. Disproportional reporting reflects relative frequency in the database, not actual harm, and is subject to channelling and detection bias; this exploratory signal warrants prospective study with individual-level temporality and dechallenge/rechallenge data."

Journal • CNS Disorders • Dementia • ROR1

Docking Analysis of Drugs Used in the Treatment of Alzheimer's Disease, Using Cell Membrane Receptors and Enzymes of the Kynurenine Pathway: A Pilot Study. (PubMed, Int J Mol Sci) - "All the drugs tested docked to the kainic acid receptor for glutamate, whereas donepezil, galantamine, tropisetron and N-acetylcysteine docked to the glutamate-NMDA receptor, but none docked to the glutamate-AMPA receptor...Donepezil docked to kynurenine monooxygenase, while rivastigmine, memantine and tropisetron docked to kynurenine aminotransferase-2...Despite their strong docking ability to IDO1 and TDO, none of the compounds tested inhibited their enzyme activity in an assay of kynurenine production. This pilot study highlights the varied pharmacological profile of drugs used in AlzD and suggests that a detailed examination of their functional effects should be considered to assist understanding of their different profiles at on- and off- target sites in human treatment."

Journal • Alzheimer's Disease • CNS Disorders • Pain • IDO1 • PCK2 • TDO2

The Effect of Rivastigmine on Enhanced Glucose Metabolism and Enhanced Synaptic Plasticity in the Hippocampus of Aged Rats: A Sex-Dependent Study. (PubMed, Int J Mol Sci) - "No significant differences were found between the groups in other parameters. The findings suggest that rivastigmine administration has limited effects on hippocampal insulin signaling pathways, glucose metabolism, and protein expression related to synaptic function, and that these effects may vary depending on gender."

Journal • Preclinical • DLG4 • SIRT1 • SLC2A4

A Systematic Review of Effects of Cholinesterase Inhibitors and Memantine on Cognitive Domains in Alzheimer's Disease. (PubMed, J Geriatr Psychiatry Neurol) - "Cholinesterase inhibitors (ChEI) (donepezil, rivastigmine and galantamine) and memantine have been the mainstay treatment and have showed their effectiveness on total cognitive scores, but their effects on individual cognitive domains remain unclear. Overall, higher treatment doses were consistently associated with greater preservation of cognitive function across domains.DiscussionChEIs and memantine provide domain-specific cognitive benefits beyond global cognitive improvement. Future studies should examine whether treatment tailored to domain-specific deficits improves patient outcome.PROSPEROCRD42024493998."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Current Clinical Evidence on Nose-to-Brain Drug Delivery. (PubMed, Drug Discov Today) - "Recent clinical studies investigating intranasal formulations of rivastigmine, insulin, and olanzapine, among other drugs, have provided encouraging evidence supporting the clinical translation of this delivery strategy. In addition, FDA-approved intranasal products indicated for central nervous system disorders, including diazepam and midazolam for seizure management, and triptans for migraine, demonstrate the growing clinical relevance of intranasal drug delivery...Intranasal administration is non-invasive, painless, and may improve patient adherence while enhancing brain bioavailability. Nevertheless, further well-designed clinical studies are required to establish the long-term safety, efficacy, and clinical applicability of this delivery strategy."

Journal • Review • Alzheimer's Disease • CNS Disorders • Epilepsy • Migraine • Mood Disorders • Movement Disorders • Multiple Sclerosis • Pain • Parkinson's Disease • Psychiatry

A comprehensive assessment of cholinesterase inhibitors for the treatment of Alzheimer's disease based on drug selection recommendations for Chinese Medical Institutions. (PubMed, Expert Rev Pharmacoecon Outcomes Res) - "This study aimed to comprehensively evaluate the overall clinical value of seven ChEI formulations (donepezil tablets, rivastigmine capsules, rivastigmine patches, galantamine tablets, galantamine orally disintegrating tablets, and two huperzine A formulations) to provide evidence-based guidance for rational AD pharmacotherapy selection. The remaining four drugs may be prescribed according to individual patient conditions and institutional available resources. This evaluation provides evidence-based guidance for clinical and institutional decision-making in AD management and delivers a generalizable assessment framework adaptable to local real-world data for healthcare institutions globally."

Journal • Alzheimer's Disease • CNS Disorders

Overcoming acidic limitations: an Os-Ru bimetallic polymeric nanozyme at neutral pH for dual-mode detection of acetylcholinesterase activity and its inhibitors. (PubMed, J Mater Chem B) - "The platform achieves ultrasensitive acetylcholinesterase (AChE) detection (LOD = 0.0297 mU mL-1 for colorimetry and 0.0856 mU mL-1 for fluorometry) and reliable inhibitor analysis (IC50 = 0.716 µM and 0.92 µM for the clinical drug rivastigmine tartrate), outperforming most reported neutral-pH AChE assays. Beyond analytical performance, this study establishes a generalizable design principle for decoupling nanozyme catalytic efficiency from pH constraints, establishing a versatile framework for physiologically adaptive, multimodal biosensing with broad implications in neurodegenerative diagnostics and drug discovery."

Journal • CNS Disorders • Pain

Lead optimization of rivastigmine-like hybrids: Impact of nitro group and halogen substitution on multi-target anti-Alzheimer's activity. (PubMed, Bioorg Med Chem) - "Hybrid 2 showed inhibitory activity against hAChE close to that of donepezil (IC50 = 0.029 ± 0.005 μM), while 7 had better activity against eqBChE than the parent drug rivastigmine (IC50 = 0.45 ± 0.02 μM). Cyano-derivative 8 appears to be the only compound with preserved multi-enzymatic inhibitory potential, even without nitro-group in its structure and can be used as starting point for further series. Finally, many hybrids demonstrated interesting experimental pharmacokinetic properties, evaluated using bioanalytical methods."

Journal • Alzheimer's Disease • CNS Disorders

Clinical Studies Using Intranasal Therapies for Parkinson's Disease: A Review. (PubMed, Adv Pharm Bull) - "intranasal glutathione was safe and showed better bioavailability...Intranasal cholecystokinin and ipratropium bromide did not show significant benefits. Intranasal desmopressin is a safe and effective medication for nocturnal polyuria in Parkinson disease...Finally, Rivastigmine nasal spray offered better bioavailability and fewer side effects compared with conventional forms...This review highlights the potential applications, efficacy, and side effects of various intranasal medications for Parkinson's disease and proposes using new interventions for future studies. The general benefits of nasal administration for Parkinson's disease treatment include localized effects, fewer side effects, faster onset of action, improved bioavailability, and enhanced therapeutic effectiveness."

Journal • Review • CNS Disorders • Hypoglycemia • Movement Disorders • Otorhinolaryngology • Parkinson's Disease • Transplantation

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups. (PubMed, J Affect Disord) - "Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups."

Journal • Retrospective data • Review • Bipolar Disorder • CNS Disorders • Mood Disorders • Pediatrics • Psychiatry

Synthesis, Biological Evaluation, Molecular Docking and Molecular Dynamics of Substituted Thieno[2,3-d]pyrimidine Derivatives as Potential Anti-Alzheimer Agents. (PubMed, Int J Mol Sci) - "Structural confirmation was achieved using spectroscopic techniques, and biological evaluation was performed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with donepezil and rivastigmine as reference drugs. Structure-activity relationship analysis confirmed that nitrogen-containing substituents and cyclic amino moieties enhance potency, whereas bulky aromatic groups reduce activity. These findings establish thieno[2,3-d]pyrimidine derivatives as promising candidates for the development of next-generation anti-Alzheimer agents."

Journal • Alzheimer's Disease • CNS Disorders • Pain

Cumulative Anticholinergic Burden and Risk of Delirium Among Older Adults with Alzheimer's Disease. (PubMed, Pharmacy (Basel)) - "This retrospective cohort study used 2013-2017 Medicare claims data, and included adults 65 years and older with AD who initiated any of the ChEIs (donepezil, rivastigmine, and galantamine) after a 12-month washout period. Among older adults with AD initiating ChEIs, moderate and high CAB were associated with an increased risk of delirium compared with low/no CAB. These findings highlight the need to carefully reduce the CAB, especially dose and duration, along with utilizing anticholinergic alternatives in older adults with AD."

Journal • Alzheimer's Disease • CNS Disorders • Psychiatry

Prognostic Factors for Postictal Agitation After Electroconvulsive Therapy in Older Adults With Depression. (PubMed, Acta Psychiatr Scand) - P=N/A | "This study identified sex, flumazenil use, seizure duration, the amount of seizures during a session, and education level as prognostic factors for PIA. The pronounced clustering of PIA events within a small subset of patients suggests meaningful interindividual vulnerability, but should be replicated in future studies. If confirmed, these findings could provide actionable insights for preventive treatment strategies. In particular, the use of flumazenil should be critically reconsidered in persons experiencing PIA."

Biomarker • Journal • Anesthesia • CNS Disorders • Depression • Epilepsy • Mood Disorders • Psychiatry

Analysis of the Efficacy of Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease, Literature Review. (PubMed, Int J Mol Sci) - "Evidence from key trials indicates that standard AChEIs induce significant cognitive stabilization compared to placebo, with rivastigmine maximizing daily living parameters via transdermal delivery...Conversely, emerging agents like huperzine A and the translation-blocker Posiphen demonstrate disease-modifying potential by modulating CSF biomarkers associated with amyloid and tau proteins. Clinically, while traditional regimens are limited by gastrointestinal toxicities, transitioning toward innovative multi-target structures represents a necessary shift to address both cognitive decline and neurodegeneration."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Pain

Eugenol-derived carbamates as sub-nanomolar dual cholinesterase inhibitors with neuroprotective activity against Alzheimer’s disease: Structure-activity relationships and molecular dynamics insights. (PubMed, Bioorg Chem) - "Among the synthesized compounds, E11 emerged as the most potent AChE inhibitor (IC50 = 0.62 nM), surpassing rivastigmine (0.80 nM), the only clinically approved carbamate-based inhibitor, while displaying a markedly AChE-selective profile (SI = 24.0)...In silico ADME profiling predicted favorable gastrointestinal absorption, blood-brain barrier permeability, and absence of P-glycoprotein efflux liability for all compounds. Collectively, these findings establish eugenol-based carbamates as a pharmacologically competitive and structurally accessible multifunctional scaffold for AD, with E10 and E11 identified as priority candidates for further preclinical investigation; however, the present study is limited to in vitro and in silico evaluation, and in vivo pharmacological assessment and detailed metabolic profiling, particularly regarding the predicted mild CYP450 liability of the aryl-substituted derivatives, are warranted in future studies."

Journal • Alzheimer's Disease • CNS Disorders • Pain

High-performance liquid chromatography - diode array detection method validation for amentoflavone-type biflavonoids in five Encephalartos species with potential neuroprotective activity. (PubMed, Sci Rep) - "The isolated biflavonoids (1-3) showed potent AChE inhibitory activity with IC50= 2.146 ± 0.086, 0.762 ± 0.039, and 1.474 ± 0.061 µg/mL respectively compared to rivastigmine, the positive control (IC50= 3.357 ± 0.103 µg/mL)...In addition, total phenolic and total flavonoid contents were estimated in the selected plants. This study highlights Encephalartos as a potential source of bioactive compounds for further neuroactive drug discovery research."

Journal • CNS Disorders • Pain

Comparative risk of ventricular arrhythmia and sudden cardiac death among acetylcholinesterase inhibitors in dementia: A population-based cohort study. (PubMed, Br J Clin Pharmacol) - "The risk of ventricular arrhythmia or sudden cardiac death was comparable among donepezil, galantamine and rivastigmine in older patients with dementia."

Journal • Cardiovascular • CNS Disorders • Dementia