Basic & Clinical Pharmacology & Toxicology最新文献

Current antiseizure therapy for epilepsy is only effective in about 70% of the patient population. Previous studies had shown that the addition of small amounts of tetrahydrocannabinol (THC) made cannabidiol (CBD) much more potent in the maximal electroshock seizure (MES) model. The psychotoxic effects of THC make it unsuitable as an antiseizure therapy. The current study investigated the effects of combining CBD with the non-psychotoxic cannabinoid cannabigerol (CBG) in the MES model in mice. Mice were administered (i.p.) CBD or CBG or a combination of both before undergoing the MES procedure. Dose–response and dose–toxicity curves were generated for each compound and combinations. It was found that CBG has antiseizure properties and that it potentiates the effects of CBD. By using a 1:1 ratio combination of CBD and CBG, the ED₅₀ for CBD was reduced by over 50% and the TD₅₀ for CBD was reduced by 40%, indicating increased toxicity. This suggests that the interaction between CBD and CBG may be additive in nature. Both drugs showed little toxicity at therapeutic doses. This is the first study to provide detailed dose–response data for CBG as well as CBG in combination with CBD in a seizure model and suggests that the two drugs could act in a similar manner to suppress seizures.

Climate change poses a significant challenge for global health. The World Health Organization estimates 250 000 additional annual deaths between 2030 and 2050 due to global warming. The healthcare sector is a major contributor to greenhouse gas (GHG) emissions, accounting for approximately 4.4%–5.5% of a country's total carbon footprint, with medicines contributing 5%–10%. This scoping review provides an overview of existing literature on the climate impact of medicines in the hospital sector and identifies knowledge gaps. The review followed PRISMA-ScR guidelines, conducting a comprehensive literature search in PubMed and Embase. Peer-reviewed articles published in the last 20 years, reporting original data on GHG emissions from medicines in the hospital sector were included. Articles were categorized based on therapeutic area, enabling a structured mapping of current areas of evidence. Of the 2986 studies identified, 32 were included. Most focused on emissions from inhaled anaesthetic gases (n = 15), followed by inhaler therapies (n = 6), total healthcare systems (n = 4), ophthalmology (n = 3), surgical procedures (n = 2) and other areas (n = 2). The findings show that research on the climate impact of medicines in the hospital sector remains limited. Knowledge gaps persist across most therapeutic areas, highlighting the need for research to inform climate-friendly strategies and support decision-making.

Chronic kidney disease (CKD) remains a significant global health burden despite recent advances in pharmacotherapy, including sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists. Renal fibrosis, a central pathological hallmark of CKD progression, is mediated by persistent inflammation and macrophage activation, wherein the kallikrein–kinin system—particularly kinin receptors—plays a critical role. Emerging evidence supports the therapeutic potential of dual kinin receptor antagonism, especially targeting B1R, though the precise molecular mechanisms remain incompletely understood, necessitating further investigation. To elucidate the role of kinin receptors in renal injury, male C57BL/6 mice were subjected to folic acid-induced nephropathy and treated with either the B1R antagonist R715 or the B2R antagonist HOE140. Treatments were administered pre- and postfolic acid injection. Renal function was evaluated via serum creatinine, blood urea nitrogen and urine analyses. Renal tissues underwent histopathological assessment and gene expression profiling to assess injury and fibrotic responses. B2R antagonism (HOE140) failed to attenuate acute tubular injury but ameliorated chronic damage by downregulating proinflammatory mediators and upregulating anti-inflammatory markers. In contrast, B1R blockade (R715) exacerbated acute kidney injury yet mitigated chronic fibrosis, improving renal function and reducing profibrotic gene expression. These findings delineate distinct, time-dependent roles of B1R and B2R in modulating macrophage polarization (M1/M2) and fibrogenesis, identifying potential targets for antifibrotic therapies.