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The vigilance promoting drug modafinil modulates serotonin transmission in the rat prefrontal cortex and dorsal raphe nucleus. Possible relevance for its postulated antidepressant activity.

Modafinil, (RS)-2-(diphenylmethylsulfinyl)acetamide derivative (Modiodal, Provigil), is a vigilance-promoting agent which reduces sleep episodes by improving wakefulness. It is approved by the USA FDA for narcolepsy, shiftwork sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure. Unlike classical psychostimulants such as amphetamine and amphetamine-like compounds, the awaking effect of modafinil is not associated with a disturbance of nighttime sleep, tolerance, and sensitization. Its precise mechanism of acti

Best practice in the use of natalizumab in multiple sclerosis.

Natalizumab is approved for the treatment of patients with relapsing-remitting multiple sclerosis who have failed first-line treatment with traditional disease-modifying therapies or who have highly active disease. The drug has proved highly effective, both in a clinical trial setting and in clinical practice, with marked reductions in the rate of clinical relapses and slowed disease progression. These clinical outcomes are mirrored by a marked reduction in disease activity as evidenced by magnetic resonance imaging of the brain. However, natalizumab treatment has been associated with a risk o

A phase I clinical trial of tiopronin, a putative neuroprotective agent, in aneurysmal subarachnoid hemorrhage.

BACKGROUND: The neurotoxic aldehyde 3-aminopropanal (3-AP) contributes to brain injury following cerebral ischemia. Tiopronin (N-2-mercaptopropionyl-glycine[N-2-MPG]) is a US Food and Drug Administration (FDA)-approved drug for the treatment of cystinuria and a putative neuroprotective agent that has been shown to bind and neutralize 3-AP and reduce infarct volumes. OBJECTIVE: The objective of this trial was to establish the safety of tiopronin administration in patients with aneurysmal subarachnoid hemorrhage (aSAH) in preparation for further trials of its efficacy as a neuroprotective agent

Historical control monotherapy design in the treatment of epilepsy.

PURPOSE: Monotherapy approvals have been difficult to obtain from the U.S. Food and Drug Administration (FDA), and have almost all been achieved using a trial design entitled "withdrawal to monotherapy" in treatment-resistant patients, which employs a so-called "pseudo-placebo" as a comparator arm. The authors submitted a white paper to the FDA advocating use of a virtual placebo historical control as an alternative to pseudo-placebo. Such an approach reduces patient risk that would result from exposure to pseudo-placebo. In this article, we present the data submitted to the FDA to justify a h

Total ankle replacement systems available in the United States.

Ankle replacement continues to be a viable option for treating patients with ankle arthritis. Over the past 10 years, there has been a significant increase in the number of ankle replacement systems available for use. Current controversy centers on whether fixed- or mobile-bearing devices are most advantageous. Most total ankle systems used outside the United States are mobile-bearing devices, whereas ankle replacement systems used in the United States are all essentially fixed-bearing devices. Not all ankles with degenerative changes are amenable to replacement surgery, and several exclusion

A small-molecule screen identifies the antipsychotic drug pimozide as an inhibitor of Listeria monocytogenes infection.

We developed a screening procedure to identify small-molecule compounds that altered infection by Listeria monocytogenes to gain insights into bacterial/host cellular processes required for intracellular pathogenesis. A small-molecule library of 480 compounds with known biological functions was screened, and 21 compounds that altered the L. monocytogenes infection of murine bone marrow-derived macrophages (BMM) were identified. The identified compounds affected various cellular functions, such as actin polymerization, kinase/phosphatase activity, calcium signaling, and apoptosis. Pimozide, an

Post-marketing safety surveillance of EGFR-targeted agents and disseminated intravascular coagulation risk: a disproportionality analysis based on the FDA Adverse Event Reporting System.

INTRODUCTION: The epidermal growth factor receptor (EGFR) serves as a principal therapeutic target in oncology, with EGFR inhibitors representing essential agents in cancer treatment. Although thrombotic complications related to EGFR inhibitors have been reported in the literature, the evidence remains insufficient. Notably, EGFR inhibitor-associated disseminated intravascular coagulation (DIC) constitutes a potentially fatal condition that currently lacks comprehensive systematic investigation. AIM: To systematically assess the signal and clinical characteristics of DIC potentially associate

[Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2025 edition)].

To further standardize lung cancer prevention and treatment measures in China, enhance the quality of diagnosis and treatment, improve patient prognosis, and provide evidence-based medical guidance for clinicians at all levels, the Chinese Medical Association convened experts from respiratory medicine, oncology, thoracic surgery, radiotherapy, imaging, and pathology to develop the Chinese Medical Association's Clinical diagnosis and treatment guidelines for lung cancer (2025 edition). This consensus resulted in several updates from the 2024 version. In the screening section, a new recommendati

[Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2025 edition)].

To further standardize lung cancer prevention and treatment measures in China, enhance the quality of diagnosis and treatment, improve patient prognosis, and provide evidence-based medical guidance for clinicians at all levels, the Chinese Medical Association convened experts from respiratory medicine, oncology, thoracic surgery, radiotherapy, imaging, and pathology to develop the "Chinese Medical Association's clinical diagnosis and treatment guidelines for lung cancer (2025 edition)". This consensus resulted in several updates from the 2024 version. In the screening section, a new recommenda

Targeting TROP2 Across Solid Tumors: The Clinical Profile and Role of Datopotamab Deruxtecan.

OBJECTIVE: To evaluate the pharmacology, efficacy, safety, and clinical use of datopotamab deruxtecan (Dato-DXd), a recently approved trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC), in the treatment of advanced solid tumors. DATA SOURCES: A comprehensive English-language literature search was conducted on PubMed and ClinicalTrials.gov from January 2010 through September 2025 using the search terms datopotamab, datroway, breast cancer, or nonsmall cell lung cancer. STUDY SELECTION AND DATA EXTRACTION: Evidence was gathered from clinical trials, relevant arti

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Opportunities and Challenges.

Hepatocellular carcinoma (HCC) is the most common malignancy worldwide, and is especially common in China. A total of 70%-80% of patients are diagnosed at an advanced stage and can receive only palliative care. Sorafenib has been the standard of care for a decade, and promising results for regorafenib as a second-line and lenvatinib as a first-line treatment were reported only 1 or 2 years ago. FOLFOX4 was recently recommended as a clinical practice guideline by the China Food and Drug Administration. All approved systemic therapies remain unsatisfactory, with limited objective response rates

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations.

Melanoma remains a critical public health problem worldwide. Patients with stage IV disease have very poor prognosis and their 1-year survival rate is only 25%. Until recently, systemic treatments with a positive impact on overall survival (OS) had remained elusive. In recent years, the United States Food and Drug Administration (FDA) - approved several novel agents targeting the RAS/RAF/MEK/ERK pathway (vemurafenib, dabrafenib, and trametinib) - critical in cell division and proliferation of melanoma, and an immune checkpoint inhibitor (ipilimumab) directed against the cytotoxic T lymphocyte

Delivery Characterization of SPL84 Inhaled Antisense Oligonucleotide Drug for 3849 + 10 kb C- > T Cystic Fibrosis Patients.

Recent advances in the therapeutic potential of RNA-related treatments, specifically for antisense oligonucleotide (ASO)-based drugs, have led to increased numbers of ASO regulatory approvals. In this study, we focus on SPL84, an inhaled ASO-based drug, developed for the treatment of the pulmonary disease cystic fibrosis (CF). Pulmonary drug delivery is challenging, due to a variety of biological, physical, chemical, and structural barriers, especially when targeting the cell nucleus. The distribution of SPL84 throughout the lungs, penetration into the epithelial cells and nucleus, and structu

An evaluation of pharmacological options for Cushing's disease: what are the state-of-the-art options?

INTRODUCTION: Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. Cortisol normalization is a key goal to treatment. Pituitary surgery remains the first-line approach for Cushing's disease, but sometimes it is impracticable, unsuccessful, or complicated by recurrence. Medical therapy has been historically considered a palliative. However, in the latest years, interest on this topic has grown due to both the availability of new drugs and the reevaluation of the old, commonly used drugs in clinical practice. AREAS COVERED: In this article, we will discuss t

Use of unapproved or off-label drugs in Japan for the treatment of graft-versus-host disease and post-transplant viral infection.

Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving the

A sensitive and validated HPLC-UV method for the quantitative determination of the new antifungal drug isavuconazole in human plasma.

Isavuconazole is a broad-spectrum triazole antifungal drug recently approved for the therapy of both invasive aspergillosis and mucormycosis. To support a widespread therapeutic drug monitoring of isavuconazole, a simple, sensitive, and precise high-performance liquid chromatography method with UV detection was developed and fully validated for the quantification of this drug in human plasma. The method involved a combined protein precipitation-solid-phase extraction and a chromatographic separation on a Waters XTerra RP18 (150 × 4.6 mm, 3.5 μm) column using an isocratic mobile phase of ammoni

A review of the potential role of nano-enabled drug delivery technologies in amyotrophic lateral sclerosis: lessons learned from other neurodegenerative disorders.

Amyotrophic lateral sclerosis (ALS) has a multitude of factors implicated in its etiology. The complex neuro-etiology and the restrictive nature of the blood-brain barrier (BBB) have significantly hindered the drug therapy of ALS. Riluzole, a moderately performing drug, is the only agent approved for treating ALS. However, several promising nanocarrier approaches are surfacing that can provide more efficient drug delivery. In addition, biologicals such as stem cells are able to carry neurotrophic factors to their target site, providing motor neurons with the benefits of both, stem cells and ne

Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis.

OBJECTIVES: To compare the clinical effectiveness of zaleplon, zolpidem or zopiclone (Z-drugs) with either benzodiazepines licensed and approved for use in the UK for the short-term management of insomnia (diazepam, loprazolam, lorazepam, lormetazepam, nitrazepam, temazepam) or with each other. METHODS: MEDLINE, EMBASE, PsycINFO, Science Citation Index/Web of Science were searched from 1966 to March 2003 and The Cochrane Library, reference lists of included studies and a number of psychopharmacology journals. Randomized controlled trials comparing either benzodiazepines with the Z-drugs or an

Dose Optimization of Targeted Therapies for Oncologic Indications.

Therapeutic advances in oncology in the 21st century have contributed to significant declines in cancer mortality. Notably, targeted therapies comprised the largest proportion of oncology drugs approved by the United States (US) Food and Drug Administration (FDA) over the past 25 years and have become the standard of care for the treatment of many cancers. However, despite the metamorphosis of the therapeutic landscape, some aspects of cancer drug development have remained essentially unchanged. In particular, the dose-finding methodology originally developed for cytotoxic chemotherapy drugs c

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… The FOCR study determined that PMRs to evaluate dosing variations were given a median 4.5 years for completion (from drug approval to final study report due date) [ 39 ]. … Consequently, the MTD may never be identified: an analysis of oncology drugs approved by the FDA between 2010 and 2021 found that for more than half, no MTD was determined [ 6 ]. …

DrugSpaceX: a large screenable and synthetically tractable database extending drug space.

One of the most prominent topics in drug discovery is efficient exploration of the vast drug-like chemical space to find synthesizable and novel chemical structures with desired biological properties. To address this challenge, we created the DrugSpaceX (https://drugspacex.simm.ac.cn/) database based on expert-defined transformations of approved drug molecules. The current version of DrugSpaceX contains >100 million transformed chemical products for virtual screening, with outstanding characteristics in terms of structural novelty, diversity and large three-dimensional chemical space coverage.