Mylan · CACNA1C · 小分子
verapamil 是一种小分子，由Mylan研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。
| 商品名 | verapamil, Mylan, verapamil SR, Mylan, verapamil ER |
| 公司 | Mylan |
| 药物类别 | 小分子 |
| 分子靶点 | CACNA1C |
| 给药途径 | Oral (PO) |
| 状态 | Approved |
verapamil 作用于 1 个分子靶点：
| CACNA1C | calcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2) |
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 disorders | Hypertension | ✓ Approved |
Wilken Silvana N SN, Rodrigues Diego V Santos DVS, Price Colin C, Jacobs Julia J et al.
[This corrects the article DOI: 10.1016/j.sipas.2025.100286.].
Gandhi Om H OH, Almasri Sami S, Gaston Nicholas T NT, Rashad Mohammad S MS et al.
Cerebral vasospasm following aneurysmal subarachnoid hemorrhage remains a leading cause of morbidity and mortality. Endovascular treatment with intra-arterial vasodilators is established for medically refractory vasospasm, yet medication delivery relies on manual hand-syringe injection with limited control over infusion rate and volume. In this proof-of-concept technical note, we describe a workflow innovation repurposing a dual-head programmable power injector (Nemoto PRESS DUO elite, Nemoto Kyorindo) for simultaneous contrast administration and controlled vasodilator infusion during endovascular vasospasm treatment. One chamber delivers contrast for angiographic runs, while the other contains a triple vasodilator cocktail of verapamil, nicardipine, and nitroglycerin, delivered via the injector's programmable Infusion Mode at operator-defined flow rates and volumes. This closed-system, dual-chamber architecture eliminates tableside syringe exchanges, reduces the risk of air entrainment, and enables precise, reproducible multi-agent delivery. In our experience with 9 patients (12 treatment sessions), the injector-based workflow facilitated routine use of the triple vasodilator cocktail with angiographic improvement observed in all sessions. Fluoroscopy time, radiation dose, contrast volume, and total procedural duration did not differ significantly from those of a historical manual-injection cohort, which served as a procedural workflow reference. Because the manual cohort received a different vasodilator regimen without nicardipine, the two cohorts are pharmacologically unmatched and angiographic outcomes were not compared between groups. No procedural complications related to the delivery method occurred. These preliminary findings suggest the dual-head programmable injector provides a feasible, ergonomic, and reproducible closed-system workflow for intra-arterial vasodilator delivery during cerebral vasospasm treatment, with broader applicability to other intra-arterial drug delivery settings.
Coté Anthony A, Peyronnet Rémi R, Ravens Ursula U
This historical review provides a short biographical overview of the British pharmacologist Edward Miles Vaughan Williams (1918-2016) and summarises the experimental findings which form the basis for his original definition of three classes of antiarrhythmic drug (AAD) action, i.e. class I action: Na+ channel block; class II action: suppression of sympathetic activity; class III action: prolongation of action potential duration. As a putative class IV action, central nervous system modulation was discussed. The development and approval of novel antiarrhythmic compounds subsequently required more refined subdivision of class I action and a fourth class of action, i.e. 'Ca2+ antagonism' as exemplified by verapamil. For half a century, this simple and easy to remember classification has served as an orientation for students and clinicians alike. Nevertheless, it has also been criticised for not being sufficiently systematic and for failing to predict the increased mortality when applied post-myocardial infarction for prevention of sudden cardiac death as published in the Cardiac Arrhythmia Suppression Trial. To overcome this seeming shortcoming, the consensus of the European task force led to a more extensive classification ('The Sicilian Gambit'), with complete listing of multiple actions of the individual antiarrhythmic drugs known at that time. The resulting classification was never widely embraced by cardiologists, most likely due to its inherent complexity. Recently, the original Vaughan Williams classification of AAD action has been expanded in order to reflect today's improved knowledge about arrhythmia mechanisms and to include novel targets for AAD actions, but at the same time, the basic concept that proved so useful in the clinical management remained conserved.
Deng Gang G, Liu Chenchen C, Wang Yihui Y, Ao Donghui D et al.
To evaluate the independent and interaction effects of prophylactic intra-arterial nitroglycerin-verapamil versus saline and a 6 Fr Glidesheath Slender versus a conventional 6 Fr sheath on clinical radial artery spasm during diagnostic transradial cerebral angiography. In this prospective, single-center, 2 × 2 factorial randomized trial, 255 patients undergoing diagnostic TRCA were assigned to prophylactic intra-arterial NV or saline and radial access with either GSS or conventional 6 Fr sheath (CS). The primary outcome was clinical RAS. Secondary outcomes included radial artery occlusion (RAO) and procedural outcomes. Clinical RAS occurred more frequently with GSS than with CS (33.9% vs 18.8%, P = .003). NV did not significantly reduce RAS compared with saline (29.7% vs 21.7%, P = .149). RAO was also higher with GSS (23.6% vs 11.7%, P = .022). After adjustment for prespecified covariates, GSS use remained associated with clinical RAS. In this exploratory randomized trial, prophylactic intra-arterial NV did not significantly reduce clinical RAS during diagnostic TRCA. GSS use was associated with higher rates of clinical RAS and RAO under the evaluated procedural conditions. These findings should be interpreted cautiously and require validation in future studies.
Rehman Najeeb Ur NU, Ansari Mohd Nazam MN, Karim Aman A, Tashah Abdullah Rabea AR et al.
This study was carried out to evaluate the possible gut modulatory and antibacterial activities of Myrica salicifolia root extract (Ms.Cr). Gas Chromatography-Mass Spectrometry (GC-MS) analysis was conducted for chemical profiling, while FTIR analyzed the chemical bonds. Mice were used for in vivo experiments, while possible pharmacodynamics were explored in rabbit jejunal tissues. GC-MS analysis identified 16 metabolites, while mice administered with lower doses of Ms.Cr (50 and 100 mg/kg) causes increase in the count of wet feces and the total number of fecal outputs, which was significantly reduced in the pre-atropinized mice. At higher doses of 200 and 400 mg/kg, Ms.Cr showed respective protection of 40% and 80% in mice in castor oil induced diarrhea. In jejunal tissues, lower concentrations of Ms.Cr increased the spontaneous contractions followed by complete relaxation at higher concentrations. Further, Ms.Cr caused concentration-dependent (1.0-5.0 mg/mL) relaxation of high K+-induced contractions, similar to papaverine. Preincubated jejunal tissues with Ms.Cr shifted the Ca++ concentration-response curves (CRCs) towards right with suppression of the maximum response, similar to verapamil, thus confirming Ca++ channel blocking activity. Similar to papaverine, preincubation of tissues with 3 and 5 mg/mL of Ms.Cr, caused shift in isoprenaline CRCs towards left, thus showing phosphodiesterase inhibition. Ms.Cr showed an antimicrobial effect against pathogenic gut bacteria including E. coli, Sh. sonnei, S. typhimurium and ESβL (extended-spectrum beta-lactamase)-producing E. coli. Thus, this research provides a solid foundation for the therapeutic uses of M. salicifolia in gut motility-related disorders.
Xiao Tianxiang T, Deng Mengqing M, Wang Wenxiu W, Lu Kai K
ATP-binding cassette (ABC) transporters play important roles in insecticide resistance, but their functional contributions and structural basis of substrate recognition remain poorly understood. Here, we demonstrate that ABCG9 is an important determinant of chlorpyrifos resistance in Nilaparvata lugens, a destructive rice pest throughout Asia. Verapamil synergism suggested the involvement of active efflux, and expression profiling identified ABCB7, ABCC5, and ABCG9 as constitutively upregulated in the resistant strain and inducible by chlorpyrifos. However, only RNAi-mediated knockdown of ABCG9 significantly increased chlorpyrifos susceptibility, suggesting that this transporter plays a critical role in chlorpyrifos resistance in N. lugens. Structural analysis revealed that ABCG9 adopts a canonical ABCG half-transporter architecture with a conserved N-terminal nucleotide-binding domain (NBD) and a C-terminal transmembrane domain (TMD) containing six helices. Molecular docking and dynamics simulations showed that chlorpyrifos binds within a hydrophobic pocket at the TMD cavity entrance, stabilized primarily by van der Waals interactions (ΔGvdW = -39.04 kcal/mol), with a total binding free energy of -33.46 kcal/mol. Notably, the predicted hydrogen bond was transient, whereas hydrophobic contacts persisted throughout the 100 ns simulation, highlighting the importance of dynamic approaches over static docking alone. These findings identify ABCG9 as a phase III efflux transporter completing the chlorpyrifos detoxification cascade and provide structural insights into substrate recognition by insect ABCG transporters.
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