Batenac (mibefradil) / Jazz - LARVOL DELTA

Pimozide Inhibits CatSper Activity, Impairs Hyperactivation and the Acrosome Reaction in Human Spermatozoa. (PubMed, Int J Mol Sci) - "Pimozide is an FDA approved drug known to block T-type calcium channels and which shares structural similarities with mibefradil, a proven antagonist of the CatSper channel. Experimental findings further support this, showing that pimozide inhibits CatSper activity, and impairs hyperactivation and the acrosome reaction in human spermatozoa. Overall, these results identify pimozide as a novel CatSper antagonist and propose a binding mode, offering a basis for the rational design of reversible, non-hormonal male contraceptives that target the CatSper channel."

Journal

Microenvironment T-Type calcium channels regulate neuronal and glial processes in tumor cells to promote glioblastoma growth. (PubMed, Neuro Oncol) - "The data reveal a role for microenvironment Cav3 in promoting GBM progression through regulating neuronal and glial processes. Targeting both intrinsic and microenvironment Cav3 with the inhibitor mibefradil significantly enhanced the anti-GBM effects of TMZ and radiation."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CAV3

Functional model for amelogenesis: polarization and pH sensitivity of calcium uptake in ameloblast-derived HAT-7 cells. (PubMed, Calcif Tissue Int) - "Store-operated Ca2+ entry (SOCE) was activated by store depletion, using the SERCA inhibitor thapsigargin, while TRPM7 function was evaluated using the agonists naltriben and mibefradil. Basolateral but not apical extracellular acidification reduced the basolateral SOCE-related Ca2+ entry. In summary, Ca2+ uptake mechanisms showed significant functional polarization in confluent HAT-7 monolayers, suggesting that HAT-7 cells may provide a model for transepithelial Ca2+ transport during enamel maturation."

Journal • TRPM7

Shear Stress Promotes Metastasis of Triple-negative Breast Cancer Cells Through Calcium Channel-ROS-FOS Axis. (PubMed, Int J Biol Sci) - "Mechanistically, calcium channel acts as the mechano-sensor to initiate the SS-ROS cascade, with calcium channel blockers Mibefradil and Nifedipine effectively weakening SS-ROS-induced invasiveness. Following ROS elevation, the downstream activation of p38-ELK1-cFOS and JNK-cJUN pathways subsequently increase the expression of malignancy-related genes. This metastasis-promoting SS-calcium channel-ROS-FOS axis provides new insights for combating metastatic progression in breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ATF3 • CTCs

The Role of CaV3.2 T-type calcium channels in normal hearing and acquired hearing loss. (PubMed, Cell Calcium) - "Auditory brainstem responses together with immunofluorescence and quantitative image analyses revealed elevated wave I thresholds and reduced amplitudes in 6-week-old CaV3.2 knockout (KO) compared to wildtype (WT) and heterozygous (HET) mice, despite comparable inner hair cell (IHC), IHC afferent presynaptic ribbon, and outer hair cell (OHC) densities. In aged mice, mibefradil treatment reduced OHC loss but did not preserve cochlear function. These findings suggest that embryonic CaV3.2 deletion resulted in early baseline auditory deficits, consistent with their possible developmental requirement, and did not confer protection against noise-induced or age-related hearing loss."

Journal • Otorhinolaryngology • CACNA1H • CAV3

Drug-drug interaction by metabolites: Challenges and solutions during therapeutics innovation. (PubMed, Drug Metab Dispos) - "Actually, the clinical risks of Met DDIs had been identified as gemfibrozil and mibefradil; mibefradil was withdrawn from the market because of serious adverse reactions. This review comprehensively analyzes regulatory guidelines by major authorities (National Medical Product Administration, US Food and Drug Administration, Pharmaceuticals and Medical Devices Agency, European Medicines Agency, and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use), summarizing their consensus on proactive Met DDI risk assessment while highlighting key discrepancies in scope, thresholds, and implementation requirements. Furthermore, it presents a translational evaluation strategy-from early in vitro characterization to advanced modeling approaches (physiologically based pharmacokinetic/population pharmacokinetic simulations) and optimized clinical study designs-with critical support from multiple case studies that illustrate practical..."

Journal • Review

Low-Voltage-Activated Calcium Current Contribute to the Repetitive Discharge Pattern of Vestibular Afferent Neurons (ARO 2026) - "LVA Ca2+ chanel blocckers such as Ni2+, mibefradil, TTA-P2 and Z944 were used. Our results showed that VANs possess a LVA current and that its heterogeneous expression contributes to repetitive discharge and to differentiate discharge patterns in these neurons."

Identification and Validation of Antidepressant Small Molecules Using Bioinformatics and Mouse Depression Models. (PubMed, Drug Des Devel Ther) - "This study identified 311 differentially expressed genes (DEGs) from GSE182193-associated with the PI3K-Akt, MAPK, and neurotrophic factor signaling pathways, with key genes identified via Weighted Gene Co-expression Network Analysis (WGCNA) and immune correlation analysis-and screened 5 candidate compounds via CMAP, among which pyrimethamine, pifithrin-mu, and mibefradil significantly improved depressive behaviors in chronic restraint stress (CRS) model mice by regulating key protein expression in the PI3K-Akt and neurotrophic factor signaling pathways, as shown by a 33.44%-60.32% increase in movement distance in the open field test (P < 0.01 to P < 0.001) and a 20.25%-30.19% decrease in immobility time in the forced swim test (P < 0.01 to P < 0.001). This study shows that pyrimethamine, pifithrin-mu, and mibefradil can regulate key proteins in the PI3K-Akt and neurotrophic factor pathways, improving depressive behaviors in mice and indicating their..."

Journal • Preclinical • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry • AKT1

The role and behavior of voltage-gated calcium channels annels in ischemia/reperfusion. (PubMed, Cell Signal) - "Experimental studies demonstrating the protective effects of VGCC inhibitors-such as nimodipine, mibefradil, and SNX-111-are critically evaluated along with their translational limitations. By integrating up-to-date mechanistic insights with preclinical and early clinical data, this review highlights VGCCs as promising molecular targets for preventing I/R injury. Future therapeutic strategies should focus on isoform-specific targeting, time-dependent administration, and organ-directed formulations to enhance efficacy and safety."

Journal • Review • Cardiovascular • Metabolic Disorders • Reperfusion Injury

A New Method for Antispastic Effect in Coronary Artery Bypass Grafts by Using a L- and T-Type Calcium Channel Blocker Efonidipine. (PubMed, Basic Clin Pharmacol Toxicol) - "The present study revealed a significant antispastic effect of efonidipine in the human IMA due to its effect on the expression of L-type (Cav1.2) and T-type (Cav3.1) proteins. The dual effect of efonidipine on both L- and T-type calcium channels is significantly greater than that of T-type calcium channel blockers. These findings suggest that efonidipine is an effective drug to prevent and treat vasospasm of the IMA during CABG surgery."

Journal • CAV3

Automated gait analysis indicates efficacy of T-type calcium channel inhibition for mitigation of disrupted calcium signalling in an SCA5 mouse model. (PubMed, Sci Rep) - "Mibefradil, an inhibitor of calcium channels, was also found to improve disordered β-III-/- Purkinje cell dendritic morphology in vitro. Building on these findings CatWalk analysis showed trimethadione, a selective T-type calcium channel inhibitor, but not riluzole nor verapamil, significantly improved interlimb coordination of 8-month-old β-III-/- mice. These findings highlight the CatWalk XT system as a valuable tool to assess age-dependence of motor function and that modulation of T-type calcium channels has therapeutic potential for SCAs."

Journal • Preclinical • Ataxia • CNS Disorders • Movement Disorders

Integrative analysis of signaling and metabolic pathways, immune infiltration patterns, and machine learning-based diagnostic model construction in major depressive disorder. (PubMed, Sci Rep) - "Through GSEA scoring, five upregulated pathways in the high-risk MDD group were identified, and multiple potential drugs such as Mibefradil, LY364947, ZLN005, STA- 5326, and vemurafenib were screened. By constructing an MDD diagnostic model, we predicted the key genes of MDD and the characteristic pathways associated with a higher risk of MDD. This provides new insights for risk stratification identification and offers new perspectives for the clinical application of precision immunotherapy and drug development."

Journal • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mood Disorders • Psychiatry

Targeting Ion Channels: Blockers Suppress Calcium Signals and Induce Cytotoxicity Across Medulloblastoma Cell Models. (PubMed, Bioengineering (Basel)) - "Spontaneous calcium signals were significantly reduced by mibefradil (calcium channel blocker), paxilline (calcium-activated potassium channel blocker), and thioridazine (potassium channel blocker)...In contrast, digoxin and ouabain, inhibitors of the Na/K pump, reduced the calcium signaling by over 90% in DAOY cells and induced approximately 90% cell death in DAOY cells and 80% cell death in D283 cells. However, these effects were significantly diminished in the cells derived from a patient with MB, highlighting the variability in drug sensitivity among MB models. These findings demonstrate that calcium signaling is critical for MB cell survival and that the targeted inhibition of calcium pathways suppresses tumor cell growth across multiple MB models."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor

T-type calcium channels attenuate anxiety in MPTP-treated mice through modulating burst firing of dopaminergic neuron. (PubMed, Neuropharmacology) - "In the present study, we constructed Parkinson's disease (PD) model mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and we found that intracerebroventricular injection of T-VGCC blocker (Mibefradil) alleviates the anxiety behavior and the extent of damage to DAergic neurons in MPTP-treated mice...To sum up, our research results for the first time reveal the crucial role that the burst firing of DAergic neurons in the SN mediated by T-VGCC plays in regulating anxiety behavior in PD. This discovery offers a potential therapeutic target for PD patients with anxiety."

Journal • Preclinical • CNS Disorders • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

T-type calcium channels regulate medulloblastoma and can be targeted for therapy. (PubMed, J Neurooncol) - "Our results represent a first comprehensive multi-omic characterization of T-type calcium channels in medulloblastoma and provide preclinical data for repurposing mibefradil as a treatment strategy for these relatively common pediatric brain tumors."

Journal • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

Voltage-Gated Calcium Channels and the Parity-Dependent Differential Uterine Response to Oxytocin in Rats. (PubMed, Reprod Sci) - "Dose-inhibition responses to mibefradil (TTCC inhibitor) and verapamil (LTCC inhibitor) were conducted on isolated V and PB uterine strips. Our findings suggest that TTCCs play a more important role than LTCC in the parity-dependent differential response to oxytocin. The impact of ORAI and TRP channels still needs to be evaluated, to gain a more comprehensive understanding of the relative impact of voltage-gated calcium channels vs. storage-operated calcium entry channels on this phenomenon."

Journal • Preclinical

Microenvironment T-Type calcium channels regulate neuronal and glial processes to promote glioblastoma growth. (PubMed, bioRxiv) - "The Cav3 blocker drug mibefradil synergized with temozolomide (TMZ) and radiation to reduce in vivo tumor growth and prolong animal survival. Conclusions Together these data reveal a role for microenvironment Cav3 in promoting GBM tumor progression through regulating neuronal and glial processes particularly associated with the OPC-cell state. Targeting both intrinsic and microenvironment Cav3 with the inhibitor mibefradil significantly enhanced the anti-GBM effects of TMZ and radiation."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CAV3 • OLIG2 • SOX10

The role of LHb T-type calcium channel in the neuropathic pain-depression comorbidity (IASP 2024) - "Mibefradil was used to observe the changes of LHb neurons excitability and the functional of T-type calcium channels in electrophysiological experiments... The SNC model can cause the occurrence of NP-depression comorbidity and the T-type calcium channel of LHb neurons is an ion channel which involved in the formation of NP-depression comorbidity and the regulation of pain and depression. T-type calcium channel is an important target for the treatment of NP-depression comorbidity."

CNS Disorders • Depression • Mood Disorders • Neuralgia • Pain • Psychiatry

Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes. (PubMed, Int J Mol Sci) - "We found that cardiotoxic drugs withdrawn due to adverse drug reactions, including encainide, mibefradil, and cetirizine, exhibited toxicity in hPSC-CMs but not in HEK293-hERG cells. The observed changes in calcium dynamics following drug exposure demonstrated the utility of hPSC-CMs as a versatile model system for assessing both cardiotoxicity and drug efficacy. Overall, our findings highlight the potential of hPSC-CMs in advancing drug discovery and development, which offer a physiologically relevant platform for the preclinical screening of novel therapeutics."

Journal • Cardiovascular

ROLE OF L- AND T-TYPE VOLTAGE-DEPENDENT CALCIUM CHANNELS IN THE HIERARCHICAL ORGANIZATION OF DEFENSIVE RESPONSES TO ELECTRICAL STIMULATION OF THE RAT DORSOLATERAL PERIAQUEDUCTAL GRAY. (PubMed, Neuropharmacology) - "Accordingly, here we investigated the effects of microinjection of lower doses (0.7 and 7 nmol) of both verapamil and mibefradil, a preferential blocker of T-type calcium channels, on DPAG-evoked defensive behaviors of the male rat. While galloping was not attenuated by either antagonist, jumping was unexpectedly attenuated by 0.7 nmol verapamil only. These results suggest that T-type calcium channels are involved in the low-threshold freezing responses of exophthalmia and immobility, whereas L-type calcium channels are involved in the trotting response that precedes the full-fledged escape responses of galloping and jumping."

Journal • Preclinical • Ophthalmology

Lavandula angustifolia Mill. inhibits high glucose and nicotine-induced Ca2+ influx in microglia and neuron-like cells via two distinct mechanisms. (PubMed, Biomed Pharmacother) - "Ca2+ influx in neuron-like cells pretreated with HG plus nicotine was also significantly decreased by LEO, an effect partially inhibited by the L-type Ca2+ channel blocker nifedipine and the T-type Ca2+ channel blocker mibefradil. LEO or a two-fold increase in the applied number of astrocytes attenuated Ca2+ influx caused by high glucose and nicotine in the mixed cells of the microglia, neuron-like cells and astrocytes. These findings suggest that LEO can regulate HG and nicotine-induced Ca2+ influx into microglia and neurons through two distinct mechanisms."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Cav3.2 channel regulates cerebral ischemia/reperfusion injury: a promising target for intervention. (PubMed, Neural Regen Res) - "T-type calcium channel blockers, such as pimozide and mibefradil, have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury. These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling. Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury."

Journal • Cardiovascular • CNS Disorders • Diabetes • Inflammation • Reperfusion Injury • Vascular Neurology • CAV3 • NFATC1 • NFATC3

Analgesic Buxus alkaloids with Enhanced Selectivity for the Low-Voltage-Gated Calcium Channel Cav3.2 over Cav3.1 through a New Binding Mode. (PubMed, Angew Chem Int Ed Engl) - "Animal studies in wild-type and Cav3.2 knock-out mice revealed that BXSL (5 mg/kg), by inhibiting Cav3.2, exhibits an analgesic effect equivalent to Z944 (10 mg/kg) or mibefradil (10 mg/kg). Moreover, we proposed a structural rationale for 9(10/19)abeo-artane-type alkaloids towards their high selectivity of Cav3.2 over Cav3.1. This study introduces a novel analgesic agent and valuable molecular insights for structure-based innovative Cav3.2 drug development."

Journal • CNS Disorders • Epilepsy • Essential Tremor • Movement Disorders • Pain • CAV3

Modulation of FDG Uptake by Cell Cycle Synchronization Using a T-Type Calcium Channel Inhibitor. (PubMed, Cancers (Basel)) - "Cell cycle synchronization could be used to increase the diagnostic sensitivity of clinical FDG positron emission tomography."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Combination treatment of calcium channel antagonist mibefradil enhances the effect of hydroxyurea at therapeutic ranges in high-grade meningioma in vitro. (SNO 2023) - "FDA-approved VGCC antagonists nimodipine (NIMO) and mibefradil (MIB) target two different VGCCs, L- and T-type channels, and have been of great interest for their use in combination therapy in other cancers...We cultured CH-157MN and IOMM-Lee MN cells and assessed their cell survival, apoptosis, and proliferation in the presence of temozolomide, octreotide, sunitinib, or hydroxyurea (HU)...Here we demonstrate for the first time that T-type calcium channels play an important role in MN survival. The combination of HU and MIB suggests their use could be a promising treatment for high-grade MN."

Preclinical • Brain Cancer • CNS Tumor • Meningioma • Oncology • Solid Tumor