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verapamil (verapamil, Mylan / verapamil SR, Mylan / verapamil ER)

✓ Approved

Mylan · CACNA1C · Small Molecule

What is verapamil?

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

Drug Profile

Brand Namesverapamil, Mylan, verapamil SR, Mylan, verapamil ER
CompanyMylan
Drug ClassSmall Molecule
Molecular TargetCACNA1C
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Mylan

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

PubMedNaunyn-Schmiedeberg's archives of pharmacology2026-11-06

Prokinetic effect of ferulic acid ethyl ester on gastrointestinal motility in mice: an integrated in silico and in vivo study.

de Carvalho Lima Izabela Borges IB, de Oliveira Marcos Meneses MM, da Costa Douglas Soares DS, Dos Santos Polyanna Negreiros PN et al.

Gastrointestinal paralysis and dysmotility remain clinically relevant conditions associated with delayed intestinal transit, feeding intolerance, prolonged hospitalization, and limited effective pharmacological treatment options. Among these disorders, postoperative ileus (POI) is a common complication after abdominal surgery characterized by transient suppression of coordinated gastrointestinal motility. The present study investigated the effects of ferulic acid ethyl ester (FAEE) on intestinal motility and explored its underlying mechanisms using integrated in silico and in vivo approaches. Gastrointestinal transit was assessed in mice by the charcoal meal test under normal conditions and in an experimental POI model induced by intestinal manipulation. In normal mice, FAEE (50 and 100 mg/kg, p.o.) significantly increased intestinal transit. In POI animals, FAEE (50 mg/kg) significantly attenuated the postoperative delay in intestinal transit. Biochemical analyses showed that FAEE reduced MPO activity, NOx, and MDA levels, while restoring SOD activity and GSH content. Pharmacological studies further indicated that the prokinetic effect of FAEE involves cholinergic and calcium-dependent pathways, as atropine and verapamil significantly attenuated its effects. In contrast, pharmacological blockade of opioid and 5-HT3 receptors did not significantly alter the prokinetic effect of FAEE under the present experimental conditions. Molecular docking predicted favorable binding of FAEE to M3R and CaV1.2. In conclusion, FAEE exerts prokinetic effects and attenuates the development of postoperative dysmotility, with findings suggesting the involvement of cholinergic and calcium-dependent pathways and an association with anti-inflammatory and antioxidant effects.

PMID 42993219
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PubMedAnnals of translational medicine2026-11-06

First in vivo evaluation of pharmaceutical modulation of porcine ureteral distensibility.

Tano Zachary E ZE, Wu Yi-Xi YX, Gao Bruce M BM, Cumpanas Andrei D AD et al.

Pharmacologic relaxation of ureteral smooth muscle may promote spontaneous stone passage via medical expulsive therapy (MET), reduce renal colic, and facilitate ureteroscopic access to the kidney. We evaluated the effects of six oral smooth muscle relaxants on porcine ureteral distensibility using the novel University of California, Irvine (UCI) force sensor. Thirty-five juvenile female Yorkshire swine contributed 59 evaluable ureters following 7 days of oral treatment with placebo, fasudil, mirabegron, Rowatinex®, silodosin, tadalafil, or verapamil. Distensibility was measured as maximum dilator size passed and ureteral size scale (USS). Generalized estimating equations accounted for bilateral ureters and adjusted for age, baseline bacteriuria, and the corresponding day zero measurement. Primary analyses estimated within-group changes of ureteral distensibility due to fasudil, mirabegron, silodosin, tadalafil, and control, with a Holm correction performed across ten tests. Secondary analyses compared adjusted changes among groups and versus the control group. Untreated controls showed minimal change in ureteral size (+0.2 Fr, P=0.84) or USS (+0.8 points, P=0.73). In the primary, within-group analysis, and before multiplicity correction, fasudil increased ureteral size by 0.78 Fr (P=0.02) and USS by 3.39 points (P<0.001). After Holm correction, only the fasudil-associated USS increase remained significant (adjusted P=0.004). Sensitivity analysis using each group's observed baseline characteristics supported increases with fasudil in size (+0.93 Fr) and USS (+3.48 points), both significant after correction. In the secondary analysis comparing medication groups to control, which was underpowered and had unbalanced baseline characteristics, no medication differed significantly from control after correction. Oral fasudil showed the strongest association with increased porcine ureteral distensibility. These findings warrant an appropriately powered direct comparison between fasudil-treated and untreated control animals. Given the clinical tolerability and safety of fasudil, the findings could also support a clinical evaluation of oral fasudil for MET and ureteral colic in carefully selected patients.

PMID 42991443
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PubMedPhytomedicine : international journal of phytotherapy and phytopharmacology2026-11-06

Activity of the natural biflavonoid hinokiflavone against multidrug-resistant CEM/ADR5000 leukemia cells and its modes of action via P-glycoprotein modulation.

Lei Xiao X, Taghizadeh Daria Shiva DS, Klauck Sabine M SM, Hai Yuanping Y et al.

Multidrug resistance (MDR), frequently associated with the overexpression of ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), is a major obstacle to successful leukemia chemotherapy. Natural products represent an important source for anticancer drug discovery. Hinokiflavone, a natural biflavonoid, has demonstrated anticancer potential, but its underlying mechanisms against multidrug-resistant leukemia are largely unknown. We hypothesized that hinokiflavone exhibits preferential activity against P-gp-overexpressing multidrug-resistant leukemia cells through specific mechanisms associated with the multidrug-resistant phenotype. Cytotoxicity was evaluated in parental and drug-resistant cell models, and the contribution of ABCB1/P-gp to the collateral sensitivity of CEM/ADR5000 cells was investigated by siRNA-mediated ABCB1 knockdown. Molecular docking was performed to predict potential interactions with both P-gp and breast cancer resistance protein (BCRP). mRNA-based transcriptomic expression profiling, Western blot analysis, pathway analyses, and siRNA-mediated TXNIP knockdown were used to investigate signaling alterations. Intracellular ROS generation, mitochondrial membrane potential, P-gp-associated drug transport, ATP levels, cell cycle distribution, DNA damage, and apoptosis were further investigated. In addition, a zebrafish xenograft model was used to evaluate preliminary in vivo antitumor activity. Hinokiflavone exhibited collateral sensitivity toward P-gp-overexpressing CEM/ADR5000 leukemia cells, and ABCB1 knockdown markedly reduced this sensitivity. Moreover, hinokiflavone significantly restored doxorubicin sensitivity in multidrug-resistant CEM/ADR5000 cells, reducing the IC₅₀ of doxorubicin by 3.17-fold, comparable to the P-glycoprotein inhibitor verapamil. Molecular docking predicted interactions with both P-gp and BCRP. Transcriptomic and protein analyses revealed alterations in several signaling pathways (activated WNT/β-catenin signaling, increased TXNIP and PTEN expression, and reduced PI3K/AKT/mTOR signaling). TXNIP knockdown attenuated the effects of hinokiflavone on PI3K/AKT/mTOR signaling and reduced the cytotoxic response. Hinokiflavone treatment was also associated with ROS accumulation, mitochondrial membrane depolarization, altered P-gp-associated drug transport, ATP depletion, G2/M-related cell-cycle alterations, DNA damage, and apoptosis. Hinokiflavone additionally exhibited preliminary antitumor activity in an SK-N-DZ zebrafish xenograft model. Hinokiflavone exhibits collateral sensitivity in P-gp-overexpressing CEM/ADR5000 leukemia cells, with ABCB1/P-glycoprotein contributing substantially to this phenotype. Its activity is associated with oxidative stress, energy metabolism, P-gp-associated drug transport, and multiple survival signaling pathways. These findings highlight hinokiflavone's potential for targeting multidrug-resistant leukemia.

PMID 42994334
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PubMedBioanalysis2026-11-05

Simultaneous LC-MS/MS quantification of four KRAS inhibitors (RMC-6236, RMC-9805, RMC-7977, and MRTX1133) in human plasma: toward therapeutic drug monitoring in pancreatic ductal adenocarcinoma.

Sabbioni Gabriele G

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, with KRASG12D mutations present in approximately 40-45% of cases. Emerging RAS(ON) inhibitors, including RMC-6236, RMC-9805, RMC-7977, and MRTX1133, offer a promising precision medicine alternative to nonspecific chemotherapy. However, except for MRTX1133, published methods for quantifying these compounds in human plasma or blood remain unavailable. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of RMC-6236, RMC-9805, RMC-7977, and MRTX1133 in human plasma. Plasma proteins were precipitated with ethanol using reserpine, verapamil, and labetalol as internal standards. Before LC-MS/MS analysis, 4,4'-methylenebis(2,6-diethylaniline) was added as a volumetric standard. Volumetric and internal-standard quantification produced comparable results. Due to matrix effects, analytes should be quantified using calibration curves prepared in spiked plasma. The method showed excellent linearity, with r2 > 0.991, across 0.1-50 ng per 0.1 mL plasma. The lower limit of quantification from spiked plasma (0.1 mL) was 0.1 ng for RMC-6236, RMC-9805, and RMC-7977, and 0.02 ng for MRTX1133. This first simultaneous assay for multiple KRASG12D inhibitors in human plasma supports pharmacokinetic studies and biomarker-driven PDAC clinical trials.

PMID 42988458
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PubMedStem cell research & therapy2026-11-05

Wnt5a/Ca2+ signal promotes myogenic differentiation by mediating a slow and sustained influx of Ca2.

Wang Mao-Yuan MY, Cao Jin-Guo JG, Zhong Yan-Biao YB, Luo Yun Y et al.

The extracellular Ca2+ is crucial for the regeneration of skeletal muscles, but there is still uncertainty regarding the channels through which it enters the cells. The purpose of this study is to investigate how the Wnt5a/Ca²⁺ signaling pathway promotes myogenic differentiation by regulating which calcium channels on the cell membrane. Myogenic regulatory factors (MRFs) play an important regulatory role in the occurrence and development of skeletal muscle, while overexpression or knockdown of Wnt5a can affect the expression levels of MRFs. Increased expression of Wnt5a resulted in significant increase of intracellular Ca2+ levels, and knockdown of TRPC3 could partially reverse the effect of Wnt5a. This indicates that in addition to the TRPC3 channel, there are other Ca2+ channels involved in the process of transporting extracellular Ca2+ into the cells. When we treated with verapamil, we found that it could significantly reduce the level of Ca2+ entering the cells, indicating that this unknown Ca2+ channel is a slow calcium channel. Through co-immunoprecipitation, we found that CaV1.1 was abundantly accumulated in the TRPC3 pull-down complex, indicating that this slow calcium channel is CaV1.1, and the expression of CaV1.1 is influenced by TRPC3. In simple terms, the activated TRPC3 activates Cav1.1, inducing a slow and sustained inward flow of extracellular Ca2+, leading to the increase of intracellular levels of Ca2+, and finally promote myogenic differentiation.

PMID 42983592
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PubMedCanadian journal of physiology and pharmacology2026-11-04

Effects of Verapamil on the Pharmacokinetics and Blood Glucose-Lowering Efficacy of Saxagliptin in Normal and Streptozotocin-Nicotinamide-Induced Type 2 Diabetic Male Rats.

Atik Orkun O, Birdane Yavuz Osman YO

Cardiovascular side effects are the leading cause of hospitalization/death in patients with diabetes. Saxagliptin is recommended for glycemic control in patients with Type-2-Diabetes-Mellitus (T2DM), while verapamil is preferred for cardiovascular disease. Although verapamil has been reported to exert blood glucose-lowering effects, its potential influence on the pharmacokinetics and glucose-lowering efficacy of saxagliptin has not yet been fully elucidated. This study aimed to investigate the effect of verapamil on the pharmacokinetics and blood glucose-lowering activity of saxagliptin in healthy and T2DM-model rats. Pharmacokinetic profiles of oral administration of saxagliptin (20 mg/kg) in rats with four groups (two healthy and two diabetic), with or without pretreatment of verapamil (10 mg/kg/day, PO, for 7 days), were examined. Also, blood glucose levels were analyzed to determine pharmacodynamic differences. Verapamil significantly increased the peak plasma concentration of saxagliptin in healthy and diabetic rats (from 4.8±1.07 to 6.96±1.22 μg/mL and from 6.05±1.68 to 8.24±1.2 μg/mL, respectively). Additionally, it was determined that blood glucose levels decreased with saxagliptin administration in all groups, and the decrease was higher in the verapamil-pretreated groups. The findings of this study may assist identify the best pharmacological combination effects of verapamil and saxagliptin in the treatment of diabetes.

PMID 42981591
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