Drug Database
VE

verapamil (Verelan Chrono / Veralan / Veratensin)

✓ Approved

Takeda · CACNA1C · Small Molecule

What is verapamil?

verapamil is a small molecule developed by Takeda. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesVerelan Chrono, Veralan, Veratensin
CompanyTakeda
Drug ClassSmall Molecule
Molecular TargetCACNA1C
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Takeda

Mechanism of Action

Molecular Targets

verapamil acts on 1 molecular target:

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

verapamil is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

Related Research Articles

PubMedFrontiers in medicine2026-10-14

Radial artery characteristics before and after intra-arterial administration of nitroglycerin and verapamil: an optical coherence tomography study.

Wang Senhu S, Zhou Jia J, He Saiying S, Liu Hao H et al.

Radial artery dimensions before and after intra-arterial vasodilator administration remain incompletely characterized along the vessel. This study used optical coherence tomography (OCT) to assess paired changes in mean lumen diameter. Twelve patients underwent baseline OCT 5 min after limited sheath insertion and post-administration OCT after intra-arterial nitroglycerin and verapamil, before coronary angiography. The full OCT-imaged radial artery span was divided into equal proximal, middle, and distal thirds before selecting anatomically matched analyzable portions. Analysis included 1,482 matched cross-sectional pairs (2,964 frames), with a cumulative matched analyzable length of 1,404.4 mm. Measurements at matched 1-mm intervals were aggregated within patients. Mean lumen diameter was the representative lumen metric; area and volume were supportive measurements. Mean lumen diameter increased from 3.06 ± 0.49 to 3.35 ± 0.56 mm (mean paired change, 0.29 mm; 95% CI, 0.20-0.39; P < 0.001). The mean patient-level relative increase was 9.6%. Mean increases were observed in all three thirds in exploratory analyses. Mean radial artery lumen diameter was greater after intra-arterial nitroglycerin and verapamil than at baseline. https://www.chictr.org.cn/hvshowproject.html?id=270,922&v=1.1, Chinese Clinical Trial Registry (ChiCTR) ChiCTR2500097574.

PMID 42871015
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PubMedCirculation. Arrhythmia and electrophysiology2026-10-12

Multichannel Dysfunction Associated With a Dominant-Negative KCNH2 Missense Variant, p.G604S, Results in Action Potential Duration Prolongation and Early Afterdepolarizations in a Patient-Specific, Reengineered Cardiomyocyte Model of Type 2 Long-QT Syndrome.

Huynh Trung T, Ye Dan D, Zhou Wei W, Tester David J DJ et al.

Type 2 long-QT syndrome results from KCNH2-encoded Kv11.1 loss-of-function, but whether secondary inward-current dysfunction amplifies dysfunction remains unclear. We characterized sodium (SCN5A, INa) and L-type calcium channel (CACNA1C, ICa) function in KCNH2-G604S and variant-corrected isogenic control induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Whole-cell patch-clamp measured action potential duration at 90% repolarization (APD90), and potassium (IKr), sodium (INa), and calcium (ICa, L) currents. Fluo-4 imaging quantified calcium transients. A modified Kernik-Clancy iPSC-CM model incorporated experimentally measured persistent INa,L and ICa,L fractions and simulated isolated and combined current defects. KCNH2-G604S caused severe IKr loss-of-function (72.5% reduction). APD90 was prolonged in G604S-iPSC-CMs (765±58 ms) compared with isogenic controls (368±37 ms; P<0.005), with early afterdepolarizations in 50% of G604S cells. Nifedipine, verapamil, and mexiletine successfully shortened APD90 and abolished early afterdepolarizations. Compared with isogenic control, INa,L (0.60±0.1% versus 0.26±0.06%; P<0.01), persistent ICa,L (2.88±0.55% versus 1.26±0.35%; P<0.05), and calcium transient decay times (P<0.0001) were greater in G604S iPSC-CMs. Increased persistent ICa,L was phenocopied by E-4031 in isogenic controls and reduced by nifedipine in G604S iPSC-CMs. In silico modeling revealed that the IKr defect alone prolonged APD90 to only 620 ms. The addition of the observed INa,L defect had a small additive effect (+20 ms); however, incorporating persistent ICa,L synergistically extended APD90 to 758 ms, replicating the experimental phenotype. Flux dynamics analysis indicated that this persistent Ca2+ entry suppresses the forward-mode sodium-calcium exchanger, forcing a compensatory reliance on sarcoplasmic-endoplasmic reticulum Ca-ATPase that primes for calcium instability. The KCNH2-G604S variant drives a severe multihit phenotype via primary IKr loss-of-function and secondary state-dependent gain-of-function in persistent ICa,L. These comprehensive validations demonstrate that the remodeled persistent ICa,L acts as the essential amplifier driving extreme action potential duration prolongation and Ca2+ mishandling.

PMID 42861500
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PubMedAntioxidants & redox signaling2026-10-07

Identification of Thioredoxin-Interacting Protein as an Upstream Regulator of Ferroptosis in Hyperuricemic Nephropathy.

Xi Yuemei Y, Wang Qiang Q, Liu Yayan Y, Huang Shuai S et al.

Hyperuricemic nephropathy (HN) is a major contributor to chronic kidney disease, yet current urate-lowering therapies often fail to halt tubular injury once established. While ferroptosis is known to drive renal injury in HN, the upstream molecular mechanisms remain unclear. We investigated whether thioredoxin-interacting protein (TXNIP) acts as an upstream regulator linking hyperuricemia to ferroptosis-associated tubular injury in HN. TXNIP expression was examined in renal biopsies from patients with HN and two murine models (drug-induced and Uox-/- mice). Functional studies combined pharmacological suppression of TXNIP expression using verapamil with genetic validation in a novel Uox-/-Txnip-/- double-knockout model. Renal injury and ferroptosis-associated alterations were assessed using biochemical, molecular, histological, ultrastructural, and transcriptomic analyses. TXNIP was markedly upregulated and predominantly localized to renal tubular epithelial cells in both murine models and patients with HN. Verapamil-associated suppression of TXNIP expression attenuated renal dysfunction, tubular injury, inflammation, and interstitial fibrosis without significantly reducing serum urate. The novel Uox-/-Txnip-/- model provided direct genetic evidence that TXNIP contributes to the hyperuricemic renal phenotype. Across the pharmacological and genetic approaches, renal protection was accompanied by reduced tubular iron accumulation and lipid peroxidation, restoration of glutathione (GSH) content and xCT/GPX4 expression, decreased ACSL4 expression, and attenuation of ferroptosis-associated mitochondrial abnormalities. These findings identify TXNIP as an upstream regulator of ferroptosis-associated tubular injury in HN and provide genetic evidence for its contribution to the hyperuricemic renal phenotype. The pharmacological findings further suggest that targeting TXNIP-associated injury pathways may complement conventional urate-lowering therapy. Antioxid. Redox Signal. 00, 000-000.

PMID 42844223
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PubMedFrontiers in pharmacology2026-10-06

Calcium channel blocker-associated pulmonary toxicity: epidemiology, mechanisms, and clinical management.

Jiang Qiu Q, Cui Wen-Hui WH, He Jia-Yi JY, Xie Zhi-Qi ZQ et al.

Calcium channel blockers are first-line medications for the treatment of hypertension, angina pectoris, and arrhythmias, and are generally well-tolerated. However, in recent years, there have been reports indicating that CCBs may cause severe pulmonary toxicity, such as non-cardiogenic pulmonary edema and acute respiratory distress syndrome. This article employs a comprehensive review methodology to systematically summarize the clinical types, incidence, risk factors, mechanisms of injury, and management strategies for CCB-related pulmonary toxicity. Current evidence indicates that pulmonary toxicity is extremely rare at standard therapeutic doses; however, the incidence increases significantly in cases of acute overdose and among specific populations (pregnant women, patients with underlying cardiopulmonary diseases). Pharmacovigilance studies have identified significant signals suggesting an association between nifedipine, diltiazem, and verapamil to pulmonary edema, with amlodipine having the highest number of related clinical reports. Major risk factors include drug overdose, pregnancy, underlying cardiopulmonary disease, and differences among CCB subclasses. Toxicity associated with dihydropyridine CCBs is primarily characterized by vasodilatory shock, whereas non-dihydropyridine CCBs exhibit a combination of cardiac depressant and vasodilatory effects. Mechanisms involve hemodynamic changes, increased capillary permeability, inflammatory activation, and alveolar epithelial dysfunction. Early recognition, drug discontinuation, selection of vasoactive agents based on the type of shock, and life support are key to improving prognosis.

PMID 42835333
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PubMedNuclear medicine communications2026-10-05

Dynamic 99mTc-MIBI uptake and washout as functional biomarkers of glycyrrhizic acid-induced mitochondrial dysfunction and P-glycoprotein activity in HepG2 cells.

Al-Saeedi Fatma J FJ, Sohrabi Farah Y FY, Aryan Dana A DA, Marafi Fatema F FF et al.

To investigate the effects of glycyrrhizic acid on HepG2 cell viability and the cellular uptake, retention, and washout kinetics of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI), with particular emphasis on the potential involvement of mitochondrial function and P-glycoprotein (P-gp)-mediated efflux. HepG2 cells were treated with glycyrrhizic acid at concentrations ranging from 0 to 100 μM, and cell viability was assessed using the MTT assay. Cellular 99mTc-MIBI uptake was evaluated over 5-120 min to characterize time-dependent tracer accumulation. Pulse-chase experiments were performed to assess intracellular tracer retention and washout over 30-180 min following tracer loading. The contribution of P-gp-mediated efflux was further investigated by assessing the effect of the P-gp inhibitor verapamil on intracellular 99mTc-MIBI accumulation in glycyrrhizic acid-treated cells. Glycyrrhizic acid reduced HepG2 cell viability in a concentration- and time-dependent manner, with an IC50 of approximately 60 μM after 48 h. In untreated cells, 99mTc-MIBI accumulation progressively increased and approached a plateau between 60 and 120 min. Glycyrrhizic acid treatment reduced intracellular tracer uptake in a concentration-dependent manner. Pulse-chase experiments demonstrated decreased intracellular tracer retention and increased washout following glycyrrhizic acid treatment. Pretreatment with verapamil partially increased intracellular 99mTc-MIBI accumulation compared with glycyrrhizic acid treatment alone, indicating that P-gp-mediated efflux may contribute to the reduced tracer retention observed after glycyrrhizic acid exposure. Glycyrrhizic acid alters 99mTc-MIBI uptake, intracellular retention, and washout kinetics in HepG2 cells. The observed changes are consistent with altered mitochondrial tracer sequestration and increased transporter-mediated efflux, although the present findings do not establish these mechanisms directly. Dynamic 99mTc-MIBI kinetics may therefore provide a functional approach for assessing cellular responses to glycyrrhizic acid, warranting further mechanistic and in-vivo validation.

PMID 42831255
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PubMedMaterials today. Bio2026-10-04

Intensity-dependent microcurrent stimulation enhances BMSC-derived cartilage microtissue formation under defined culture conditions.

Fei Xiang X, Wu Hao H, Li Mengxing M, Xu Yong Y et al.

Engineering phenotypically favorable cartilage-like tissue from bone marrow mesenchymal stem cells (BMSCs) remains challenging because chondrogenic differentiation can be accompanied by insufficient cartilage-associated extracellular matrix accumulation and unfavorable hypertrophic and catabolic responses. Here, we established a microcurrent-assisted culture system for scaffold-free BMSC-derived cartilage microtissues (CMTs) and investigated the intensity-dependent effects of continuous unidirectional direct-current stimulation at 0, 50, 100, 150, 250, or 500 μA under a defined electrical and culture configuration. Among the tested conditions, 150 μA (nominal electrode current density, 3 μA/mm2) showed the most consistently favorable overall response, with enhanced cartilage-associated gene and protein expression, greater type II collagen- and glycosaminoglycan-rich matrix accumulation, improved CMT morphology, and higher apparent mechanical properties. In contrast, 250 and 500 μA were associated with reduced cartilage-associated matrix formation and increased fibrotic, hypertrophic, catabolic, inflammatory, and apoptosis-related markers. The 150 μA condition was also associated with a distinct intracellular Ca2+ response pattern and increased NFATc1 nuclear localization; verapamil, BAPTA-AM, and cyclosporin A attenuated NFATc1 nuclear localization, supporting involvement of Ca2+/calcineurin/NFAT-related signaling without establishing a unique causal mechanism. After 2 weeks of xenogeneic subcutaneous implantation in nude mice, CMTs preconditioned at 150 μA exhibited greater cartilage-like matrix accumulation and higher apparent compressive properties than those preconditioned at 0 or 500 μA. These findings identify 150 μA as the best-performing tested condition under the present electrical configuration and provide short-term ectopic proof-of-concept evidence, while longer-term orthotopic studies are required to evaluate phenotypic stability, tissue integration, and functional outcomes in cartilage-defect models.

PMID 42828103
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