British Journal of Pharmacology最新文献

Mechanopharmacology is an emerging interdisciplinary field that investigates drug action using biomechanically appropriate in vitro systems to the relevant (patho)physiology. This review outlines emerging technologies and techniques which aim to bridge the gap between mechanical cues influencing cellular biology and conventional pharmacology. We delve into the impact of mechanopharmacology on drug development in cancers and fibrotic diseases. Mechanical cues such as stretch, stiffness, circadian rhythms, fluid flow, intercellular signalling cascades and cytoskeletal structures can modulate drug interactions with molecular targets with implications for drug discovery and development. Models incorporating mechanopharmacological cues to investigate pharmacokinetics, pharmacodynamics and therapeutic outcomes are outlined. Furthermore, this review discusses innovations in the use of biomaterials and microfluidics to further enable the emulation of the mechanical microenvironment. We advocate for the application of mechanopharmacological considerations to improve the physiological relevance of methods used in the drug discovery pipeline.

Psychedelic drugs are under active consideration for clinical use and have generated significant interest for their potential as anti-nociceptive treatments for chronic pain, and for addressing conditions like depression, frequently co-morbid with pain. This review primarily explores the utility of preclinical animal models in investigating the potential of psilocybin as an anti-nociceptive agent. Initial studies involving psilocybin in animal models of neuropathic and inflammatory pain are summarised, alongside areas where further research is needed. The potential mechanisms of action, including targeting serotonergic pathways through the activation of 5-HT_2A receptors at both spinal and central levels, as well as neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain, are considered. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Also discussed is psilocybin's profile as an ideal anti-nociceptive agent, with a wide range of effects against chronic pain and its associated inflammatory or emotional components.

Drug development for children presents unique challenges and is highly regulated. Novel approaches, such as the use of extrapolation to address, for example, the need to avoid unethical studies, whilst supporting robust evidence generation have been developed in support of benefit/risk considerations by regulatory authorities. This is only one step in the decision-making process towards access, which in Europe also includes health technology assessment (HTA) bodies.

Discussions related to evidentiary requirements in small populations using scientific evidence transfer have been identified as a priority action by European Medicines Agency/European Network for Health Technology Assessment 21 (EMA/EUnetHTA 21). We describe the outcome of this work and reflect on the discussions that had taken place on how to leverage prior knowledge through identifying and addressing uncertainties during life cycle management to support regulatory and HTA decision-making. Using examples, we explore the range of applications for evidence generation and offer regulatory and HTA insights on key design considerations for producing better evidence, reflecting our shared ambition. Early interactions with all respective stakeholders, particularly between regulators and HTA bodies are key to optimise data generation and utility in children.

In Europe, the HTA regulation will offer opportunities for collaborations, which are important for all development efforts. We collaboratively explored the unique specific challenges relating to paediatric drug development, ethically and in its ability to leverage prior knowledge, as exemplified using extrapolation. Learnings from these offer opportunities to further develop methodology on how to leverage uncertainties across a product's life cycle for small populations generally.