isradipine / Generic mfg. - LARVOL DELTA

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

Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials. (PubMed, Parkinsonism Relat Disord) - "Further validation using data sets with frequent administration of MDS-UPDRS is necessary to assess value of this approach as an outcome measure in PD clinical trials."

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

Bullous IgA Vasculitis: A Unique Presentation and Potential Marker of Severity (AAP-NCE 2024) - "She was started on lisinopril with as needed isradipine for hypertension.On day one of admission, she developed severe periumbilical pain, without evidence of intussusception on ultrasound, and was started on methylprednisolone...Her rash began improving on day four and she was discharged home on lisinopril, furosemide, and prednisolone... By being aware of this unique presentation of bullous IgA vasculitis, unnecessary skin biopsies can be avoided in patients who present with skin purpura consistent with IgA vasculitis that advances into bullae. Current evidence is nonconclusive regarding the link between severity of skin findings and renal involvement, however this unique case suggests these findings may be a useful predictor which can broaden our understanding with research into the severity of disease and skin findings on clinical presentation."

Cardiovascular • Glomerulonephritis • Hematological Disorders • Hypertension • Nephrology • Pain • Pediatrics • Renal Disease • Rheumatology • Vasculitis

Genetic signatures stratify PwP into three subgroups with differing responses in two disease-modifying Phase 3 trials and indicate multiple disease biology pathways to Parkinson's Disease (MDS Congress 2024) - "WGS and pharmacokinetic data from two disease-modifying Phase 3 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... Treatments that address the heterogeneity and complexity of PD are the most likely to benefit patients. 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."

P3 data • CNS Disorders • Parkinson's Disease

Identification and validation of diagnostic genes associated with neutrophil extracellular traps of type 2 diabetes mellitus. (PubMed, Front Genet) - "The gene-drug network included CACNA1C-Isradipine, CACNA1C-Benidipine and other relationship pairs. FGF1 and AGER were markedly regulated downwards in the T2DM group. Through bioinformatic analysis, we identified NETs-related diagnostic genes (ITIH3, FGF1, NRCAM, AGER, CACNA1C) in T2DM, and explored their mechanism of action from different aspects, providing new ideas for the studies related to diagnosis and treatment of T2DM."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • AGER • CACNA1A • MIR455 • STAT1

A Novel De Novo Gain-of-Function CACNA1D Variant in Neurodevelopmental Disease With Congenital Tremor, Seizures, and Hypotonia. (PubMed, Neurol Genet) - "Despite retained sensitivity to the Ca2+ channel blocker isradipine in vitro, no beneficial effects of isradipine or nifedipine treatment were observed in the index case. Through this report, we expand the knowledge about the disease presentation in patients with CACNA1D variants and show the novel variant's modulatory effects on CaV1.3 gating."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Endocrine Disorders • Epilepsy • Genetic Disorders • Hypoglycemia • Movement Disorders • Otorhinolaryngology • Psychiatry • Respiratory Diseases • CAV1

IATRO: Impact of Antihypertensive Therapy on Recurrence Risk of Ovarian Cancer for Bevacizumab-associated Hypertension (clinicaltrials.gov) - P=N/A | N=9464 | Active, not recruiting | Sponsor: Groupe Hospitalier Pitie-Salpetriere

New trial • Cardiovascular • Hypertension • Oncology • Ovarian Cancer • Solid Tumor

Targeting calciumopathy for neuroprotection: focus on calcium channels Cav1, Orai1 and P2X7. (PubMed, Cell Calcium) - "Thus, a recent CT tested whether isradipine, a blocker of the Cav1 subtype of voltage-operated calcium channels (VOCCs), exerted a benefit in patients with Parkinson's disease (PD); however, outcomes were negative...Thus, by targeting the three channels with a combination of three drug blockers we expect favorable changes in some of the pathogenic features of NDDs, namely (i) to mitigate Ca2+ entry into microglia; (ii) to decrease the Ca2+-dependent microglia activation; (iii) to decrease the sustained neuroinflammation; (iv) to decrease the uncontrolled Ca2+ entry into neurons; (v) to rescue vulnerable neurons from death; and (vi) to delay disease progression. In this review we discuss the arguments underlying our triad hypothesis in the sense that the combination of three repositioned medicines targeting Cav1, Orai1, and P2X7 calcium channels could boost neuroprotection and delay the progression of AD and other NDDs."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CAV1

L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure. (PubMed, Neuropharmacology) - "In female and male rats, systemic administration of the LTCC blocker isradipine (0.4 mg/kg and 1.2 mg/kg, I.P.) attenuated the CUS-induced decrease in sucrose preference and reversed the CUS-induced decrease in open arm time...However, there were no significant differences in forced swim test immobility time between HCC and CUS exposed animals. Taken together, these data point to a role of LTCCs in the regulation of mood disorder-related behavioral phenotype responses to chronic stress exposure."

Journal • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

Drugs for hypertension. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Review • Cardiovascular • Hypertension

Enhanced isradipine sensitivity in vascular smooth muscle cells due to hypoxia-induced Cav1.2 splicing and RbFox1/Fox2 downregulation. (PubMed, FEBS J) - "Overexpression of RbFox1 and RbFox2 successfully reduces isradipine sensitivity in hypoxic smooth muscle cells. Our results suggest a new strategy to manage ischemic diseases such as stroke and myocardial infarction."

Journal • Cardiovascular • Hypertension • Myocardial Infarction • RBFOX1

Isradipine augmentation of virtual reality cue exposure therapy for tobacco craving: a triple-blind randomized controlled trial. (PubMed, Neuropsychopharmacology) - P1 | "The findings of the current study support follow-up clinical trials that specifically test the efficacy of isradipine-augmented VR-CET for reducing smoking relapse rates after an initial quit attempt. clinicaltrials.gov: NCT03083353."

Journal • Cardiovascular • Hypertension • Pain

The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets. (PubMed, iScience) - "Blocking isradipine-sensitive L-type voltage-gated Ca2+ (Cav) channels abolished α-cell electrical activity but had little impact on its cytosolic Ca2+ oscillations or low-glucose-stimulated glucagon secretion...ω-Agatoxin IVA blocked α-cell ER Ca2+ release and cell exocytosis, but had no additive effect on glucagon secretion when combined with ryanodine. We conclude that glucose regulates glucagon secretion through the control of ER Ca2+ mobilization, a mechanism that can be independent of α-cell electrical activity."

Journal • Preclinical • Hypoglycemia

Novel protocol for multiple-dose oral administration of the L-type Ca2+ channel blocker isradipine in mice: A dose-finding pharmacokinetic study. (PubMed, Channels (Austin)) - "This procedure does not require animal handling, allows repeated drug application over several days and reproducibly achieves peak plasma concentrations over a wide range previously shown to be well-tolerated in humans. This protocol should facilitate ongoing nonclinical studies in mice exploring new indications for DHP Ca2+ channel blockers."

Journal • PK/PD data • Preclinical • Pain

Isradipine, an L-type calcium channel blocker, attenuates cocaine effects in mice by reducing central glutamate release. (PubMed, Eur J Pharmacol) - "Notably, the gene expression of ionotropic glutamate receptors, AMPA, and NMDA, remained unchanged, as did the expression of Cav1.2 and Cav1.3 channels. Importantly, these findings suggest that LTCC blockage may inhibit behavioral responses to cocaine, most likely by decreasing glutamatergic input in areas related to addiction."

Journal • Preclinical • CNS Disorders • Psychiatry • Substance Abuse • CACNA1D