isradipine / Generic mfg. - LARVOL DELTA

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

Pharmacokinetic Variability of Direct Oral Anticoagulants and Calcium Channel Blockers: A Comparative Analysis of Exposure Data from Clinical Studies. (PubMed, Pharmaceutics) - "Among DOACs, edoxaban exhibited the lowest PK variability, whereas dabigatran showed the highest. CCBs demonstrated a broad variability spectrum, ranging from predictable agents (amlodipine and felodipine) to highly variable compounds (nisoldipine, isradipine, nimodipine, diltiazem, and verapamil)... These findings suggest that fixed-dose strategies may not be universally appropriate for DOACs and CCBs, particularly in high-risk subgroups where altered exposure may lead to sub- or supratherapeutic concentrations and compromise clinical outcomes. Therefore, clinicians should avoid evaluating individual risk factors in isolation and instead consider the patient's complete profile when selecting and adjusting pharmacotherapy."

Journal • PK/PD data

Structure-based drug repurposing and in vitro evaluation of VAV2-associated candidates for suppression of macrophage foam-cell formation in atherosclerosis. (PubMed, Mol Divers) - "Virtual screening, molecular docking, ADMET prediction, three independent 200-ns molecular-dynamics simulations, principal-component analysis, and MM-PBSA calculations prioritized talazoparib, tivozanib, and isradipine for further evaluation. These findings provide preliminary computational and cellular support for further investigation of the selected compounds. However, direct binding to or inhibition of VAV2 has not been demonstrated and requires biochemical, genetic, pharmacological, and in vivo validation."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

Mechanism of fatty acid uptake and inhibition in human FATP2. (PubMed, bioRxiv) - "These findings provide a structural framework for understanding vectorial fatty acid channeling and a scaffold for developing modulators of metabolic flux. Cryo-EM structures of human FATP2 reveal a membrane-anchored lollipop topologyEndogenous fatty acids within a hydrophobic tunnel delineate the fatty acid uptake pathwayIsradipine and benidipine displace fatty acids to trap a non-productive conformationAcyl-CoA product inhibition may provide negative feedback via steric occlusion."

Journal • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • SLC27A2

Pediatric Extra-Adrenal Pelvic Paraganglioma with SDHB Mutation: A Rare Case Presenting Diagnostic and Management Challenges (ENDO 2026) - "Isradipine, labetalol, and doxazosin were given at that time with symptomatic improvement. This case underscores diagnostic delays due to subtle and episodic symptomatology, the surgical challenges posed by complex pelvic anatomy resulting in positive margins, and the critical importance of postoperative surveillance. Because SDHB mutations carry a high risk for malignancy, lifelong biochemical and radiographic surveillance is mandatory. This case further highlights the value of multidisciplinary coordination and long-term surveillance in hereditary endocrine syndromes, where both risk of recurrence and quality-of-life outcomes must be carefully managed."

Clinical • Cardiovascular • CNS Disorders • Endocrine Disorders • Hypertension • Neuroendocrine Tumor • Pediatrics • Sleep Disorder • Solid Tumor • SDHB

Estradiol Regulates LTCC-Dependent Social Behavior Deficits During Cocaine Abstinence in Female Rats (ENDO 2026) - "Social preference was assessed using a three-chamber social interaction test, with systemic isradipine (1.2 mg/kg, i.p.) administered 15 minutes prior to testing...These findings demonstrate that estradiol does not simply protect against abstinence-related social deficits but rather biases neural signaling such that social behavior becomes sensitive to LTCC-dependent mechanisms. This work identifies a functional estradiol–LTCC interaction regulating social motivation during cocaine abstinence and highlights the importance of hormonal state in shaping sex-specific addiction vulnerability."

Late-breaking abstract • Preclinical • CNS Disorders

In silico screen identifies Pranidipine as a potential inhibitor of the PD-1/PD-L1 immune checkpoint. (PubMed, Sci Rep) - "Among the screened compounds, Pranidipine, Isradipine, and Efonidipine exhibited the most favorable binding profiles toward PD-1/PD-L1 complex inhibition...Collectively, our in silico findings suggest that selected DHP-CCBs may represent promising repurposing candidates for targeting the PD-1/PD-L1 immune checkpoint. However, further in vitro studies are required to validate their potential biological activity."

Journal • Oncology

Distinct pathways in idiopathic Parkinson’s: Three genetic subgroups with distinct clinical trajectories and different treatment responses in two phase III trials (WPC 2026) - "A unique genetic signal was identified that stratified PwP into 3 distinct subgroups A/B/C. Multiple novel subgroup-specific risk variants/SNPs were identified, strongly suggesting differing disease mechanisms between the subgroups. To test this hypothesis, we analysed two Phase III trials that targeted different proposed disease mechanisms but had not found efficacy: (i) STEADY-PD3, testing the calcium channel blocker isradipine; (ii) SURE-PD3, testing increased serum urate levels."

Clinical • P3 data • CNS Disorders • Movement Disorders • Parkinson's Disease

A high-throughput screening platform to facilitate treatment development in Rett syndrome. (PubMed, Front Neurol) - "Among the candidate drug hits, isradipine, a dihydropyridine calcium-channel blocker, provided preliminary evidence of neuroprotective effects both in vitro and in vivo...siRNA knockdown of LRRC17 not only rescued mitochondrial dysfunction in RTT astrocytes but also reversed deficits in neurons cultured in astrocyte-conditioned media. Our study provides new insights into mitochondrial dysfunction in RTT and establishes an HTS platform for the initial identification of novel therapeutic targets for follow-up studies."

Journal • CNS Disorders • Developmental Disorders • Metabolic Disorders • Movement Disorders • Psychiatry • LRRC1

Targeted Putaminal CaV1.3-shRNA Gene Therapy in Aged Parkinsonism Male and Female Macaques Demonstrates Reversal of Longstanding Parkinsonian Behavioral Deficits and Evidence of Nigrostriatal Dopamine Restoration (ASGCT 2026) - "However, clinical trials repurposing the dihydropyridine isradipine (CaV1.2/1.3 antagonist) failed to show therapeutic efficacy...The beneficial SN characteristics of our gene therapy, together with presumed putaminal restoration of neuronal architecture and circuitry, provides a first-ever dual therapeutic benefit by critically targeting both SN DA neurons and their target. Given the high disease modifying/restorative therapeutic potential of our RNAi studies, in a second follow-up study, we are now conducting a lead-optimization study in young adult NHPs, comparing CaV1.3 knockdown efficacy between shRNAs and microRNA expressed in the context of an AAV genome suitable for human use (NIH NS110398)."

Gene therapy • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease • CACNA1D • CAV1

Population pharmacokinetics of isradipine in children with acute hypertension (ANZCTR) - P=N/A | N=30 | Not yet recruiting | Sponsor: Child and Adolescent Health Service

New trial • Cardiovascular • Hypertension

Selective Cav1.3 inhibition promotes survival of transplanted dopaminergic neurons via the CaMKII-p65-p53 pathway. (PubMed, Stem Cell Reports) - "Cav1.3 inhibitors including isradipine and cp-PYT significantly reduced apoptosis and improved mDAN survival in both interferon gamma (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-induced inflammatory models, as well as in the 6-OHDA-induced toxic model in vitro...Moreover, we showed that cp-PYT treatment enhanced mDAN survival while reducing mature graft volume post-transplantation. Therefore, Cav1.3 inhibition may represent a clinically relevant strategy to enhance the survival of human pluripotent stem cell (hPSC)-derived mDANs in cell therapy for PD."

Journal • CNS Disorders • Movement Disorders • Oncology • Parkinson's Disease • Transplantation • CAV1 • IFNG • TNFA

Isradipine enhancement of virtual reality cue exposure therapy is effective for individuals with higher baseline cue-induced craving. (PubMed, Drug Alcohol Depend Rep) - "Results suggest isradipine enhances VR-CET, particularly for individuals with higher baseline levels of cue-induced craving. Future studies testing prevention strategies that target higher cue-induced craving with isradipine to reduce rates of smoking recurrence are warranted."

Journal • Tobacco Cessation

Stability of Compounded Isradipine Suspension in Different Suspending Vehicles (ASHP 2025) - No abstract available

Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers With Post-Stroke Pneumonia: A Real-World Retrospective Cohort Study (clinicaltrials.gov) - P=N/A | N=13656 | Not yet recruiting | Sponsor: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine

New trial • Real-world evidence • Cardiovascular • Infectious Disease • Pneumonia • Respiratory Diseases

Impact of antihypertensive treatment on cardiovascular event reduction in patients with asymptomatic carotid artery stenosis: a systematic review and meta-analysis. (PubMed, Pan Afr Med J) - "The results reported that enalapril and fosinopril demonstrated dual benefits in blood pressure (BP) reduction and vascular remodeling, though meta-analysis showed statistically insignificant improvements in regional cerebral blood flow (CI: -0.84, 6.08, P = 0.14, I2= 94%). Similarly, isradipine, lacidipine, and amlodipine improved carotid hemodynamics and cerebral perfusion, with meta-analysis favoring calcium channel blocker intervention for blood pressure management (CI: -3.25 to 7.64, P = 0.43)...Moreover, beta-blockers showed specific benefits, with metoprolol improving plaque echogenicity (57.3 ± 16.8 vs. 51.8 ± 20.0, p = 0.006) and reducing cardiovascular events (17% vs. 37% placebo, p = 0.011), while labetalol effectively managed post-endarterectomy hypertension. In conclusion, antihypertensive treatments showed varying effectiveness in cardiovascular event reduction and improvements in vessel measures."

Clinical • Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Hypertension

Exploring Novel Therapeutic Avenues: Drug Repurposing for Neurodegenerative Movement Disorders. (PubMed, Curr Drug Res Rev) - "Several studies on the potential of pre-existing drugs such as isradipine, tetracycline, ambroxol, metformin, deferiprone, simvastatin, etc., which have been repurposed for neurodegenerative movement disorders, including Parkinson's disease, Huntington's disease, Alzheimer's disease, Multiple Sclerosis, etc. have been discussed. Further, the current scenario and future prospective of drug repurposing have also been touched upon."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease • Movement Disorders • Multiple Sclerosis • Parkinson's Disease

Therapeutic innovation through drug repurposing: A multidimensional approach toward treating Parkinson's disease. (PubMed, Bioorg Chem) - "Ongoing research is actively investigating several repurposed drugs originally intended for different conditions, including anti-hypertensives (isradipine, dexmedetomidine), anti-asthmatics (montelukast), phosphodiesterase5 inhibitors (sildenafil), antimicrobials (rifaximin), and various CNS-active agents (aripiprazole, escitalopram, paroxetine, venlafaxine, duloxetine, caffeine). While drug repurposing holds considerable promise, comprehensive preclinical and clinical studies are essential to validate these candidates for PD-specific therapeutic applications. This review aims to provide an in-depth overview of PD, encompassing its pathological and molecular characteristics, and to critically evaluate the current landscape of drug repurposing strategies to develop effective therapies for PD."

Journal • Review • Alzheimer's Disease • Asthma • CNS Disorders • Immunology • Inflammation • Movement Disorders • Parkinson's Disease • Respiratory Diseases

Experimental and computational approaches for evaluating molecule interactions with equilibrative nucleoside transporters 1 and 2. (PubMed, J Pharmacol Exp Ther) - "This resulted in the identification of the Food and Drug Administration-approved drugs isradipine, avanafil, and istradefylline as inhibitors of ENT1. We have screened over 1600 diverse molecules, allowing us to build machine learning models that in turn were further used to make predictions to validate the models. Our combined experimental and machine learning approach resulted in the identification of multiple Food and Drug Administration-approved medications as inhibitors of ENT1 or ENT2."

Journal • Infectious Disease • Oncology • SLC29A1 • SLC29A2

Therapeutic Potential of Calcium Channel Blockers in Neuropsychiatric, Endocrine and Pain Disorders. (PubMed, Cells) - "In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes...However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines."

Journal • Review • Bipolar Disorder • Cardiovascular • CNS Disorders • Depression • Diabetes • Endocrine Disorders • Inflammation • Metabolic Disorders • Mood Disorders • Oncology • Pain • Psychiatry • Schizophrenia • Solid Tumor

L-type calcium channel blockade attenuates cue-induced cocaine-seeking in female rats. (PubMed, Behav Brain Res) - "Following a 10-day cocaine self-administration and a 14-day forced abstinence period, the rats were tested for cue-induced cocaine-seeking after receiving systemic administration of isradipine, a non-selective LTCC inhibitor (0.0mg/kg, 0.1mg/kg, 0.4mg/kg, or 1.2mg/kg, i.p.)...These results highlight the translational potential of LTCCs as a therapeutic agent to reduce relapse risk in cocaine-dependent individuals. This study underscores the importance of considering sex-specific mechanisms in addiction treatment and calls for further research into LTCCs as a target for relapse prevention."

Journal • Preclinical • CNS Disorders • Psychiatry

GENETIC SIGNATURE STRATIFIES PD PATIENTSINTO 3 SUBGROUPS WITH DIFFERING RESPONSES IN TWO PHASE 3 TRIALS AND INDICATE MULTIPLE DISEASE BIOLOGY PATHWAYS TO PD. (ADPD 2025) - "WGS and pharmacokinetic data from two disease-modifying PhaseIII trials, where testing of isradipine (STEADY-PD3) or inosine/urate (SURE-PD3) did not show efficacy in early-stage PD, were modelled for treatment and exposure effects for multiple clinical outcomes in each of the 3 subgroups...We have identified a genetic signature, relevant to PD, that stratifies PwP into three subgroups. When applied to clinical data from two previously conducted Phase 3 clinical trials, it was evident that participants with differing genetic signatures responded differently to the trial therapeutic both within and between trials."

Clinical • P3 data • CNS Disorders • Movement Disorders • Parkinson's Disease

SINGLE-MICROGLIA TRANSCRIPTOMIC TRANSITION NETWORK-BASED PREDICTION AND REAL-WORLD PATIENT DATA VALIDATION IDENTIFIES KETOROLAC AS A REPURPOSABLE DRUG FOR ALZHEIMER'S DISEASE (ADPD 2025) - "We presented a network-based drug repurposing prediction by specifically blocking transition networks from neuroinflammation like microglia (NIM) to non-NIM and we identified a set of highly repurposable drugs (i.e., ketorolac, diflunisal, bezafibrate, and isradipine) for potential treatment of AD. Using two independent real-world patient databases (MarketScan [172 million insured individuals] and INSIGHT Clinical Research Network [15 million patients]), we identified that usage of Ketorolac was associated with reduced AD incidence in both MarketScan (hazard ratio [HR] = 0.89) and INSIGHT (HR = 0.83) Clinical Research Network databases, mechanistically supported by Ketorolac-treated transcriptomic data from AD patient iPSC-derived microglia. Conclusions This study offers insights into the pathobiology of AD-relevant microglial subtypes and identifies Ketorolac as a potential anti-inflammatory treatment for AD."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • CNS Disorders • Inflammation • ADAM10 • INPP5D • PRKCA • SYK

L-type calcium channel blockade attenuates the anxiogenic-like effects of cocaine abstinence in female and male rats. (PubMed, Neuroscience) - "In summary, isradipine administration reversed the anxiogenic and increased the FST immobility time associated with cocaine abstinence in a dose and sex-dependent manner. The data underscore the importance of further investigation of LTCC mechanisms and their therapeutic potential for mood disorders associated with cocaine use disorder."

Journal • Preclinical • CNS Disorders • Mood Disorders • Psychiatry

Inactivation induced by pathogenic Cav1.3 L-type Ca2+-channel variants enhances sensitivity for dihydropyridine Ca2+ channel blockers. (PubMed, Br J Pharmacol) - "Mutations A749T and L271H induce pathogenic gating changes. Like wildtype, isradipine inhibition is strongly voltage-dependent. Our data explains their apparent higher drug sensitivity at a given negative voltage by the availability of more inactivated channels due to their more negative inactivation voltage range. Low nanomolar isradipine concentrations will only inhibit Cav1.3 channels in neurons during prolonged depolarized states without selectivity for mutant channels."

Journal • CNS Disorders • Developmental Disorders • Psychiatry • CAV1