dalfampridine / Generic mfg. - LARVOL DELTA

Printing-Assisted Integration of Thermal, Fluidic and Electrical Components in Implants for Focal Brain Cooling. (PubMed, Adv Sci (Weinh)) - "In a rodent model of epilepsy (4-aminopyridine), we demonstrate hypothermia-induced suppression of seizure-like activity. Our approach may advance the clinical translation of focal hypothermia as an alternative therapy for drug-resistant focal epilepsies."

Journal • CNS Disorders • Epilepsy

Assessment of Drug-Induced Calcium Oscillations in hiPSC-Derived Neuron-Astrocyte Cocultures Using FDSS (Neuroscience 2026) - "To evaluate the functional maturation of the neuronal networks, the following panel of pharmacological agents that induce known neuronal responses were applied to the culture at three increasing doses: the neurotransmitters glutamate and GABA, the AMPA/kainate receptor antagonist CNQX, and the ion channel modulators carbamazepine and 4-aminopyridine (4-AP).Vehicle controls (0.1% DMSO or water) produced minimal changes in either oscillation amplitude or peak frequency. These findings demonstrate that hiPSC-derived neuron-astrocyte co-cultures develop robust spontaneous network activity and exhibit reproducible, mechanism-consistent drug-induced responses that can be quantified using complementary measures of calcium oscillation amplitude and event frequency. This quantitative assay provides a scalable approach for investigating neuronal network physiology, evaluating the effects of pharmacological agents on neural excitability, and characterizing disease-associated..."

CNS Disorders

Functional ultrasound imaging-guided low-intensity focused ultrasound neuromodulation in a model of focal epilepsy (Neuroscience 2026) - "We performed intrahippocampal injections of 4-aminopyridine (4-AP) to induce epileptiform activity. LIFU stimulation of the hippocampus effectively reduced the frequency of ictal events in treated (n = 3) vs. control rats (n = 3), as measured by fUSI and concurrent EEG recordings."

CNS Disorders • Epilepsy

From de-novo molecule design to behavior and transcriptomics: An in-silico:in-vivo integrated platform for pre-screening neurodegenerative disease drugs (Neuroscience 2026) - "To validate the in-vivo pipeline, clinically informed drug selection included successful translational compounds (Levodopa, Amantadine, Pramipexole), failed phase III candidates (4-Aminopyridine, Isradipine), and Rasagiline as a translational control, given its efficacy in mammals but absence of a suitable molecular target in Drosophila. Candidates are filtered by predicted pharmacokinetic and safety profiles, then advanced into the proprietary Drosophila platform for toxicology, survival, behavior, and transcriptomic readouts, creating a closed loop in-silico:in-vivo validation. Together, this integrated platform offers a scalable, mechanistically informed strategy for pre-screening both known and de-novo molecules for neurodegenerative disease pipelines."

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Modeling neuronal diseases with automatically generated iPSC-derived dorsal forebrain 3D organoids (Neuroscience 2026) - "Benchmark compounds demonstrated expected functional responses: AMPA and 4-aminopyridine induced dose-dependent increases in oscillation frequency, while GABA reduced oscillatory activity. Additional compounds, including bicuculline, NMDA, and memantine, produced characteristic modulation of calcium signaling patterns...In addition, TBI-like conditions led to a modest decrease in cell viability after 48 hours. This integrated platform combining automated culture and advanced functional analytics demonstrates a scalable solution for disease modeling and compound screening."

CNS Disorders • Epilepsy • Vascular Neurology • GFAP

Acute Vaporized Cannabis Exposure Alters Decision-Making and Dopamine Signaling in the Nucleus Accumbens Shell During a Dynamic Foraging Task. (Neuroscience 2026) - "Grant Support NIH R01 R01MH122844; Acute Vaporized Cannabis Exposure Alters Decision-Making and Dopamine Signaling in the Nucleus Accumbens Shell During a Dynamic Foraging Task Amaya, A.M., Fisher, Z.D.G., Muir, M., McLaughlin, R.J.Cannabis use is associated with disruptions in reward-based decision-making, yet the neural mechanisms underlying these disruptions remain poorly understood...Additionally, we observed decreased post-switch adaptation, reduced sensitivity to reward contingencies, increased perseverative errors, decreased choice bias and more exploitative decision-making compared to VEH exposure. Overall, our results suggest that acute cannabis exposure alters dopamine recruitment in the NAcSh in a manner consistent with disrupted explore-exploit decision-making."

CNS Disorders

Examining neural activation in bipolar I disorder during mania: A meta-analysis of functional magnetic resonance imaging studies. (Neuroscience 2026) - "Examining neural activation in bipolar I disorder during mania: A meta-analysis of functional magnetic resonance imaging studies.Ariana Sanchez Virrueta1, Summer Herrera1, Fabiola Amaya Reyes1, Gabrielle Johnson-Venegas1, Caitlin Baten1, Gladys Zamora1, Patrick Durkee, Ph.D.,1 Ellen Woo, Ph.D.,1 Dawson Hedges, M.D.,2 Chris Miller, Ph.D.11California State University, Fresno, 2Brigham Young UniversityIntroduction: Bipolar I disorder (BD-I) is an affective disorder characterized by cycles of recurrent manic and major depressive episodes... These findings suggest that the current literature on fMRI task-based studies investigating mania are too sparse to warrant any robust conclusions. Additional studies are needed to better characterize the neural correlates of mania in BD-I."

MRI • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • GAS1

Functional parasympathetic circuits regulating ventricular electrophysiology identified by targeted neuromodulation of the ventral interventricular ganglionated plexus (Neuroscience 2026) - "Intracellular recordings from VIV-GP neurons identified key roles for 4-aminopyridine (4-AP)-sensitive voltage-gated K+ channels and apamin-sensitive Ca2+-activated K+ channels in regulating neuronal excitability...These findings identify functional parasympathetic circuits within the VIV-GP that regulate LV electrophysiological and mechanical properties. They establish the pig heart as a translational model for investigating targeted ICNS neuromodulation and support the VIV-GP as a potential therapeutic target for ventricular arrhythmias and heart failure."

CNS Disorders

Systemic administration of pramipexole and 4-aminopyridine improve the gait pattern in male taiep rats: a model of human leukodystrophy (Neuroscience 2026) - "These changes in gait parameters enhance forwardlocomotion and reduced ataxia in male taiep subjects. In base of our results, weconsider that dopaminergic D2 agonist improve gait pattern and 4-AP must improvethe transmission of action potentials at spinal central pattern generator and in thecontrol locomotor mechanism in the brainstem in this tubulinopathy rat model thatimprove gait pattern and could be useful for treatment in leukodystrophies."

Preclinical • Ataxia • CNS Disorders • Movement Disorders • TINCR

Disease-modifying effects on chronic axon damage and white matter degeneration with 4-aminopyridine after acute traumatic brain injury (Neuroscience 2026) - "These findings reveal 4-AP disease-modifying effects on the progression of evolving TBI pathology that endure long after discontinuing treatment. More broadly, these results demonstrate proof-of-concept support for developing interventions to treat axon damage and white matter degeneration."

CNS Disorders • Vascular Neurology

Augmenting Functional Recovery After Spinal Cord Injury Through a Triple-Combinatorial Intervention (Neuroscience 2026) - "The goal of our study was to investigate whether 4-aminopyridine (4-AP), a voltage-gated potassium channel blocker known to improve axonal conduction and synaptic transmission, augments Hebbian stimulation induced plasticity in humans with chronic SCI...These findings demonstrate that 4-AP potentiates Hebbian stimulation-induced plasticity and functional recovery in chronic SCI. A triple-combinatorial approach integrating neuromodulation, pharmacological facilitation, and exercise may represent a promising strategy to maximize rehabilitation outcomes."

CNS Disorders

Late-onset Alzheimer’s Disease mice show abnormally high brain excitability after focal seizure induction (Neuroscience 2026) - "Focal seizures were induced with 4-aminopyridine (4-AP; 100mM)...Our findings reveal abnormally high network excitability in the presence of late life AD-risk genes. Future work willidentify when this abnormal excitability emerges in LOAD3 model and if it has unique LFP signatures that can serve as biomarkers and can be modified by existing epilepsy strategies."

Preclinical • Alzheimer's Disease • CNS Disorders • Epilepsy

Imaging Dendritic Voltage Signals in Striatal Medium Spiny Neurons (Neuroscience 2026) - "Pharmacological blockade of A-type K⁺ channels with 4-aminopyridine significantly enhanced dendritic Ca2+ signals, indicating that local voltage-gated K⁺ conductances exert strong control over dendritic excitability. Collectively, the voltage and calcium imaging data demonstrate the presence of active electrical signaling in distal SPN dendritic branches during AP firing. These findings provide experimental constraints on dendritic integration in SPNs and establish an empirical foundation for the refinement and validation of future computational models of striatal function."

CNS Disorders

Bee Venom Reduces the Duration of 4-Aminopyridine-Induced Convulsive Seizures in Rats (Neuroscience 2026) - "These results suggest that BV has the potential to attenuate both the severity and duration of seizures, however no clear trend towards loss was observed, with only 24 hours 4-AP post-administration.Although BV has not yet been widely explored as a treatment for epilepsy, its effects on seizure modulation requires further investigation, particularly regarding its mechanisms of action within the nervous system. Supported by University of Guadalajara (PROSNI 2025, CVM/LGMC)."

Preclinical • CNS Disorders • Epilepsy • CA3

Increasing the Throughput and Complexity of Electrophysiology Readouts from Human Induced Pluripotent Stem Cell-Derived Neurons (Neuroscience 2026) - "We tested sodium (Nav) current sensitivity with 1 µM tetrodotoxin (TTX), potassium (K) current sensitivity with 1 mM 4-aminopyridine (4-AP) or 30 µM XE991, or capsaicin-sensitive current with 1 µM capsaicin. Sensory neurons were responsive to capsaicin, indicating the presence of TRPV1 receptors. We have shown that hiPSC-derived neuron activity can be measured in a high-throughput manner and across a variety of neuron subtypes, providing an automated platform for compound screening."

CNS Disorders

Pathogenic synaptotagmin-1 mutation in mouse hippocampus disrupts synaptic transmission and produces autistic behaviors (Neuroscience 2026) - "Finally, application of 4-aminopyridine (4-AP) prolonged evoked EPSC duration and partially enhanced synaptic responses in SYT1-D366E-overexpressing mice. These findings confirm that SYT1-D366E overexpression disrupts synaptic function and produces autistic behaviors. This AAV-mediated SYT1-D366E mouse model provides a valuable platform for investigating synaptic mechanism underlying SYT1-NDD and for evaluating therapeutic strategies restoring synaptic function and behavioral outcomes."

Preclinical • CNS Disorders • Mental Retardation

Mechanistical and structural basis of Kv channel inhibition by 4-aminopyridine. (PubMed, bioRxiv) - "MD simulations and mutational analysis agree with the proposed fenestration pathway and suggest that 4AP binds in its neutral form. These results support a mechanism where 4AP binds to a partially activated closed state that prevents complete activation of Kv channels, explaining its pharmacological activity."

Journal • CNS Disorders • Multiple Sclerosis

Fampridine for Symptomatic Treatment in Chronic Inflammatory Demyelinating Polyneuropathy: A Randomized, Double-Blinded, Placebo-Controlled Crossover Study. (PubMed, J Peripher Nerv Syst) - "Our study did not provide evidence that fampridine improves clinical function in CIDP patients with residual disability during stable immunoglobulin therapy. Targeting ion channel dysfunction in CIDP remains of interest, but alternative strategies may be required."

Clinical • Journal • Pain

Results from a Clinical Study of the All-Oral Regimen of CC-486 (Oral Azacitidine) and Venetoclax for Newly Diagnosed and Relapsed and Refractory Acute Myeloid Leukemia (ASH 2024) - "The MTD of CC-486 in combination with ven was previously reported as 300mg QD d1-14 in relapsed/refractory (R/R) AML (Amaya et al. High response rates have been seen in the newly diagnosed cohort with 7/7 (100%) of the patients achieving a CR/CRi, including 3/3 who harbor a TP53 mutation. Final results of the R/R cohort, as well as a larger sample size of the ND subjects, with genomic annotation, as well as translational studies exploring mechanistic differences and similarities with this all-oral regimen and conventional aza/ven, will be presented."

Clinical • Acute Myelogenous Leukemia • Anemia • Fatigue • Febrile Neutropenia • Neutropenia • Thrombocytopenia • TP53

Single Dose 4-Aminopyridine for Diagnosing Recurrent Laryngeal Nerve Paralysis Continuity After Trauma (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: Milton S. Hershey Medical Center

New P1 trial • Mood Disorders

Novel Presentation of Spinocerebellar Ataxia 27B (SCA27B): Episodic, Exercise-induced Truncal Dystonia Responsive to Dalfampridine (MDS Congress 2026) - No abstract available

Ataxia • CNS Disorders • Dystonia • Movement Disorders

Enhanced HCN-Dependent Regulation of Temporoammonic Integration and Entorhinal-Hippocampal Epileptiform Coupling Following Febrile Seizures. (PubMed, Neurochem Res) - "In the 4-aminopyridine model of induced epileptiform activity, HCN blockade increased hippocampal event burden and strengthened EC-leading temporal coupling with CA1, with particularly pronounced effects following FS. Together, these findings suggest that persistent HCN enhancement following prolonged experimental FS is associated with greater HCN-dependent regulation of temporoammonic integration and entorhinal-hippocampal coupling under 4-AP-induced epileptiform conditions."

Journal • CNS Disorders • Epilepsy • CDKN1A

The glioma metabolite, D-2-hydroxyglutarate (D-2-HG), reduces synaptic transmission and epileptiform bursts in neocortical slices. (PubMed, Exp Neurol) - "In neocortical slices with ongoing epileptiform bursts (induced by 0 Mg2+ plus 4-aminopyridine), addition of D-2-HG reduced the frequency of the bursts (prolonged inter-burst intervals) and seizure burden...Together, the results demonstrate that short-term exposure to D-2-HG inhibits seizure-like activity in neocortical slices possibly by suppressing excitatory synaptic transmission. Thus, these data do not support the initial hypothesis that D-2-HG may excite neurons and promote seizures by mimicking glutamate actions."

Journal • Brain Cancer • CNS Disorders • Epilepsy • Glioma • Low Grade Glioma • Oncology • Solid Tumor

FGF14 (GAA) repeat expansion-associated Ataxia (SCA27B): Expanding the clinical and diagnostic spectrum from the first genetically confirmed case in Argentina. (PubMed, Parkinsonism Relat Disord) - "We report the first genetically confirmed Argentinean case, initially misdiagnosed as alcoholic cerebellar degeneration. This case highlights diagnostic challenges, phenotypic heterogeneity, and the importance of genetic testing for this treatable disorder."

Journal • Ataxia • CNS Disorders • Movement Disorders

Access to hospital-based rehabilitation for people with multiple sclerosis in France: A nationwide study (2017-2023). (PubMed, Rev Neurol (Paris)) - "Access to hospital-based rehabilitation for PwMS in France remains limited and uneven, despite the expected substantial needs. Utilization is primarily driven by disease severity and availability of specialized professionals, particularly PRM, and also by territorial and sex-related disparities. These findings highlight a persistent gap between recommendations and real-world practice, underscoring the need to strengthen rehabilitation pathways, improve service availability, and integrate rehabilitation earlier in the MS care pathway."

Journal • CNS Disorders • Infectious Disease • Multiple Sclerosis