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diltiazem (Cardizem QD / Dilzem XL / Angiact)

✓ Approved

Mitsubishi Tanabe Pharma Corporation · CACNA1C · 小分子

什么是 diltiazem？

diltiazem 是一种小分子，由Mitsubishi Tanabe Pharma Corporation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Cardizem QD, Dilzem XL, Angiact
公司Mitsubishi Tanabe Pharma Corporation
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, Mitsubishi Tanabe Pharma Corporation

作用机制

分子靶点

diltiazem 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

diltiazem 针对 2 个适应症，涉及 2 个治疗领域。

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

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Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith-Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: -4.04, 95% confidence interval: -6.89 to -1.18, P = 0.006, Hedges' g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 .

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Patient versus surrogate decision making for life sustaining treatment and terminal care intensity.

Oh Tak Kyu TK, Song In-Ae IA

Physician Orders for Life-Sustaining Treatment (POLST) and Advance Directives (AD) aim to honor patient autonomy. However, the impact of the signatory's identity-whether the patient or a surrogate-on clinical trajectories in the intensive care unit (ICU) remains poorly characterized. To evaluate the association between signatory identity and terminal care intensity and hospitalization costs among adult patients in the ICU. This nationwide population-based cohort study utilized the South Korean National Health Insurance Service database, including 1,189,042 adult ICU admissions between 2020 and 2023. Statistical analyses employed high-dimensional fixed-effects models to account for institutional variability across 417 hospitals. Among 1,189,042 patients, surrogate-determined POLST (SD-POLST) was more than three times as prevalent as patient-determined POLST (PD-POLST). Among 90-day decedents, PD-POLST was associated with significantly reduced odds of invasive terminal care (OR, 0.43; 95% CI, 0.43-0.54). Conversely, SD-POLST more than doubled the odds (OR, 2.16; 95% CI, 1.98-2.35). Notably, even patients with proactive ADs experienced increased care intensity once a surrogate signed the final order (OR, 1.69; 95% CI, 1.51-1.89), indicating a phenomenon of "AD erosion." SD-POLST was also associated with significantly higher daily hospitalization costs (cost ratio, 1.04; 95% CI, 1.02-1.06) compared with no documentation. The clinical efficacy of POLST in limiting non-beneficial care depends fundamentally on the signatory. Surrogate-led decisions were associated with paradoxically higher care intensity and costs, potentially overriding prior patient wishes. These findings highlight the critical importance of early, patient-led discussions to ensure goal-concordant end-of-life care in the ICU.

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Dark matter particles with sufficiently large interactions with ordinary matter can scatter in the Earth's atmosphere and crust before reaching an underground detector. This Earth-shielding effect can induce a directional dependence in the dark matter flux, leading to a sidereal daily modulation in the signal rate. We perform a search for such a modulation using data from the SENSEI experiment, targeting MeV-scale dark matter. We achieve nearly an order-of-magnitude improvement in sensitivity over previous direct-detection bounds for dark-matter masses below ∼1  MeV, assuming the standard halo model with a Maxwell-Boltzmann velocity distribution, and restrict the amplitude of a general daily modulation signal to be below 6.8  e/g/d.

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