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verapamil (Verelan Chrono / Veralan / Veratensin)

✓ Approved

Takeda · CACNA1C · 小分子

什么是 verapamil？

verapamil 是一种小分子，由Takeda研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Verelan Chrono, Veralan, Veratensin
公司Takeda
药物类别小分子
分子靶点CACNA1C
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Takeda

作用机制

分子靶点

verapamil 作用于 1 个分子靶点：

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

verapamil 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Vascular disordersHypertension✓ Approved

相关研究文献

PubMedInternational journal of molecular sciences2026-10-27

A Conceptual Translational Bench-to-Bedside Cardiac Safety Framework for Predicting Drug-Induced QT Interval Prolongation from Molecular Structure to Clinical Data.

Sips Fianne F, Bisotti Marc-Antonio MA, Torchia Mario M, Carbone Vincenzo V et al.

QT interval prolongation is associated with an increased risk of torsades de pointes (TdP), a potentially life-threatening ventricular arrhythmia, making assessment of cardiac repolarization a critical component of drug development. This work demonstrates how integrated in silico methodologies can be used to predict and quantitatively characterize QT liability across the drug discovery and development continuum. A proof-of concept translational workflow combining molecular structure analysis, in vitro pharmacology, animal data, and clinical exposure-response modeling was evaluated using the retrospective case examples verapamil and dofetilide. Molecular structure- and pharmacology-based assessments predicted hERG channel interaction and potential QT risk for both compounds. While initial in silico analyses suggested a high QT liability for verapamil and dofetilide, mechanistic electrophysiological modeling differentiated their effects. For verapamil, concurrent calcium channel inhibition offset hERG-mediated effects, resulting in predicted reductions in action potential duration and no clinically relevant QT prolongation. In contrast, dofetilide produced concentration-dependent increases in action potential duration, consistent with its known proarrhythmic potential. Translation of nonclinical findings to humans accurately predicted the absence of clinically meaningful QT effects for verapamil and identified QT prolongation exceeding the regulatory 10 ms threshold for dofetilide at therapeutic concentrations. Drug exposure and pharmacokinetic properties could be anticipated based solely on molecular structure. This conceptual workflow demonstrates how integrated quantitative in silico approaches can support earlier identification, characterization, and communication of QT risk, enabling informed decision-making and improved development efficiency from bench to bedside.

PMID 42942081
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PubMedPakistan journal of pharmaceutical sciences2026-10-26

Unveiling the calcium channel blocking potential of Suaeda fruticosa : From ex vivo studies to molecular docking.

Saqib Fatima F, Javaid Sana S, Khan Nazima Yousaf NY, Kanwal Almas A et al.

Suaeda fruticosa is a widely distributed plant in Pakistan which has been traditionally used as a remedy for constipation, dyspnoea, headache, nausea, neurosis and vertigo. The present study aimed to scientifically validate the traditionally claimed medicinal properties of Suaeda fruticosa. The experiment involved the preparation of a 70% ethanolic extract of Suaeda fruticosa (Sf.Cr), which was tested ex-vivo in an isolated rabbit jejunum preparation for spasmolytic activity. Moreover, the crude extract was tested on isolated tracheal and aorta preparations to evaluate the effects. Sf.Cr dose-dependently relaxed the jejunum and inhibited K+(80 mM)-induced contractions with EC50 value of 0.229 mg/ml and 0.095 mg/ml, respectively. Further, the Sf.Cr caused a rightward shift in Ca2+ concentration response curves (CRCs), similar to verapamil. So, calcium channel-blocking and anticholinergic actions were responsible for the antispasmodic (anti-diarrhoeal) effect. Sf.Cr produced inhibition of carbachol (1 µM)- and K+(80 mM)-induced contractions in isolated rabbit tracheal tissues with EC50 values of 0.8339 mg/ml and 1.022 mg/ml, respectively. Sf. Cr also completely abolished the Phenylephrine (1 µM)- and K+(80 mM)-induced constrictions in isolated rabbit aortic rings, with EC50 values of 0.9448 mg/ml and 0.2026 mg/ml, respectively. Molecular docking against calmodulin (PDB ID: 6M7H) showed that 3-hydroxy-2-quinolinone attained the highest glide score (-6.742 kcal.mol-¹), establishing hydrogen bonding and Pi-Pi stacking interactions with MET124 and PHE92, surpassing the binding affinity of the standard drug verapamil (-5.464 kcal.mol-¹). SwissADME profiling showed that all identified phytoconstituents complied with Lipinski's rule of five, exhibited high gastrointestinal absorption and were predicted to cross the blood-brain barrier, supporting their oral bioavailability as drug candidates. These findings collectively established Sf.Cr as a source of non-specific calcium channel-blocking phytochemicals with potential for developing antispasmodic, bronchodilator, and vasorelaxant agents.

PMID 42929410
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PubMedCase reports in neurology2026-10-25

Reversible Cerebral Vasoconstriction Syndrome Secondary to Dermatologic Cream: A Case Report.

Wilhelm Mark Edward ME, Sessions Andrew Joseph AJ, Das Gitanjali G, Sederholm Benson H BH et al.

Imiquimod is an FDA-approved prescription topical medication used in the treatment of skin lesions and neoplasms, such as actinic keratosis, superficial basal cell carcinoma, and external genital and perianal warts. The etiology of rare CNS effects, including headache and stroke, is not completely understood. Headache is a commonly reported adverse reaction, while stroke has been identified through postmarketing pharmacovigilance reports without a definitively established causal relationship. A 60-year-old female with mild depression and basal cell carcinoma, and an absence of traditional vascular risk factors, presented with a 2-week history of new recurrent thunderclap headaches. CT angiogram showed 40-50% narrowing of the proximal right A1. Conventional angiography demonstrated multiple regions of vasoconstriction which improved with intra-arterial verapamil, supporting the diagnosis of reversible cerebral vasoconstrictive syndrome (RCVS) diagnosis. Oral verapamil was up-titrated to 40 mg every 3 h for vasospasm and headache control. At 4-week follow-up, there was only residual A1 stenosis. Pre-RCVS, the patient had been diagnosed with basal cell carcinoma and was prescribed imiquimod 5% cream, with instructions to apply one 0.25-g prefilled packet topically once daily, which she used for 8.5 weeks prior to symptom onset. The patient had been on a stable low dose (2.5 mg daily) of escitalopram, a selective serotonin reuptake inhibitor and recognized potential trigger of RCVS, for several years without prior neurological symptoms. Discontinuation after the first headache did not prevent subsequent episodes, making it less likely to be the sole precipitant, though a contributory role cannot be excluded. In the absence of other vasoactive substances or identifiable etiologies for vasculitis, we suspect that topical imiquimod was responsible for RCVS in this case. Imiquimod is an immune modulating agent that acts as a toll-like receptor (TLR) 7 agonist, causing cytokine induction, inflammatory infiltration, and tumor cell apoptosis. Though headache and stroke are reported as rare side effects, stroke subtype and etiology are uncharacterized, with no RCVS reported to our knowledge. A moyamoya animal model, a pathophysiologically distinct entity from RCVS, demonstrated that using imiquimod to induce TLR-7 activation resulted in a phenotypic change in vascular smooth muscle cells. In vivo, imiquimod also led to diminished internal carotid artery blood flow, while inhibiting TLR-7 resulted in decreased stenosis. These findings suggest that imiquimod-mediated TLR-7 agonism can directly alter cerebrovascular smooth muscle behavior - a mechanism that is biologically plausible as a contributor to the acute vasospasm observed in RCVS. Topical imiquimod is thought to trigger systemic reactions secondary to increased production and circulation of cytokines originating from dermal absorption. Further studies are warranted to evaluate the risk of topical imiquimod use as it relates to cerebral vascular emergencies. We recommend that clinicians consider systemic effects of topical medications as potential contributors to neurologic sequelae.

PMID 42923421
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PubMedResearch (Washington, D.C.)2026-10-20

Effect of Microcurrent Stimulation on Cartilage Regeneration in Engineered Chondrocyte Spheroids.

Xu Yong Y, Zheng Siqiang S, Hu Qiangsheng Q, Tao Bo B

Microcurrent stimulation has emerged as a promising biophysical cue for cartilage regeneration, but its dose-dependent effects in 3-dimensional engineered cartilage constructs remain unclear. Here, we investigated the effects of continuous direct microcurrent stimulation on auricular chondrocytes and engineered cartilage spheroids using 0-, 10-, 25-, 50-, 100-, and 200-μA stimulation for 30 min daily. In 2-dimensional culture, microcurrent stimulation did not markedly increase the DNA content or Cell Counting Kit-8 value, indicating that it did not markedly promote cell expansion or overall metabolic activity. 5-Ethynyl-2'-deoxyuridine and Ki67 assays showed that low to moderate (<50 μA) stimulation had limited effects on proliferation, whereas 100 to 200 μA attenuated proliferative activity. Nevertheless, microcurrent stimulation enhanced chondrogenic marker expression in a biphasic manner, with type II collagen, SRY-box transcription factor 9, aggrecan, and cartilage oligomeric matrix protein increasing from 0 to 50 μA and declining from 50 to 200 μA. In 3-dimensional spheroids, 50 μA produced the most favorable morphology, cartilage-specific extracellular matrix deposition, mechanical properties, and hyaline cartilage-like phenotype. Excessive stimulation increased catabolic, inflammatory, and apoptosis-associated molecular responses without causing obvious cytotoxicity, apoptosis, reactive oxygen species production, temperature change, or pH alteration. Mechanistically, 50 μA induced coordinated Ca2+ signaling and promoted nuclear factor of activated T cells (NFAT) nuclear translocation, whereas 200 μA generated dysregulated Ca2+ responses and inefficient NFAT activation. Verapamil, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, and cyclosporin A attenuated 50-μA-induced NFAT activation, supporting the involvement of the Ca2+/calcineurin/NFAT pathway. Furthermore, 50-μA-preconditioned spheroids showed superior cartilage-forming capacity after subcutaneous implantation. These findings identify 50 μA as a favorable bioelectrical stimulation condition within the tested intensity range and provide a practical strategy for enhancing cartilage spheroid maturation in cartilage tissue engineering.

PMID 42898673
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PubMedNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2026-10-18

TAC-Tic syndromes: a case series on the complex overlap between trigeminal autonomic cephalalgias and trigeminal neuralgia.

de Sousa Pelliciari Davy Henrique DH, Garcia Larissa Aguiar LA, Bordini Carlos Alberto CA, Ribeiro Jaqueline Silva JS

Trigeminal autonomic cephalalgias (TACs) and trigeminal neuralgia (TN) are classified as distinct disorders, although overlap syndromes are increasingly recognized. We retrospectively describe five women with TAC-tic overlap: two with SUNCT-tic, two with cluster-tic, and one with paroxysmal hemicrania-tic syndrome. Each had distinguishable neuralgic and autonomic pain phenotypes, appearing either simultaneously or sequentially. In both SUNCT-tic cases, repeat imaging disclosed neurovascular compression after an initially negative study; microvascular decompression produced complete remission of both phenotypes. Cluster-tic presentations were controlled with peripheral nerve blocks, carbamazepine, and verapamil. In the paroxysmal hemicrania-tic case, the autonomic component responded to indomethacin whereas the neuralgic component required neuromodulator adjustment. The opposite order of phenotype emergence in the SUNCT-tic cases, together with shifts in the dominant phenotype during treatment, supports bidirectional temporal plasticity. Convergence of trigeminal and upper cervical afferents in the trigeminocervical complex offers a plausible link between peripheral input, the trigeminal-autonomic reflex, and the observed response to occipital nerve blocks. TAC-tic syndromes are rare and probably underrecognized. Repeated phenotyping, imaging tailored to the trigeminal root when clinically indicated, and treatment directed at each component may improve clinical control.

PMID 42891854
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PubMedACS omega2026-10-17

Integrated In Silico Analysis Reveals ABC Transporter ATP-Binding Protein as a Therapeutic Target in Helicobacter pylori.

Kumar Manish M, Santosh Kumar H S HS, Kumar Ballamoole Krishna BK, Shetty Veena A VA et al.

Helicobacter pylori remains a major cause of gastric diseases, while increasing antimicrobial resistance highlights the need for novel therapeutic targets. Here, we developed a comprehensive computational target-prioritization framework integrating Rosetta Stone domain-fusion analysis, subtractive genomics, metabolic pathway mapping, structural modeling, and molecular dynamics simulations to identify pathogen-specific drug targets in H. pylori J99. Twelve conserved domain families comprising 746 proteins were identified, and domain abundance showed a weak negative correlation with versatility (r = -0.327), suggesting functional specialization through domain expansion. Sequential filtering based on essentiality, nonhomology to the human proteome and gut microbiota, subcellular localization, and druggability prioritized five candidate proteins, with the ATP-binding protein AAD06727.1 emerging as the most promising target. AlphaFold2 modeling produced a high-confidence structure containing a conserved nucleotide-binding pocket. Molecular docking identified 5'-fluorosulfonylbenzoyl-5'-adenosine (FSBA) as the highest-affinity ligand (-7.3 kcal mol-1), outperforming ATP and verapamil. Triplicate 1 μs molecular dynamics simulations of apo and halo AAD06727.1 demonstrated stable rmsd, RMSF, radius of gyration, solvent-accessible surface area, hydrogen-bond occupancy, and principal component profiles, indicating preservation of structural integrity following ATP binding. Comparative simulations with the human ABCA12 nucleotide-binding domain showed conserved global architecture while revealing distinct ligand-recognition characteristics. Together, these findings identify AAD06727.1 as a structurally stable, pathogen-specific ATP-binding protein that represents a promising candidate for future structure-guided anti-H. pylori drug development.

PMID 42889906
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