Secondary pharmacology is an essential component of drug discovery and is used extensively in the pharmaceutical industry for achieving optimal specificity of new drugs via early hazard identification and off-target mitigation. The importance of this discipline has been achieved by increasing its translational value, based on the recognition of biological target-drug molecule-adverse drug reaction (ADR) associations and integration of secondary pharmacology data with pharmacokinetic parameters. Information obtained from clinical ADRs, from recognition of specific phenotypes of animal models and from hereditary diseases provides increasing regulatory confidence in the target-based approach to ADR prediction and mitigation. Here, we review the progress of secondary pharmacology during the past decade and highlight and demonstrate its applications and impact in drug discovery.
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http://dx.doi.org/10.1016/j.drudis.2016.04.021 | DOI Listing |
PLoS Med
January 2025
Division of Psychiatry, University College London, London, United Kingdom.
Background: There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone.
Methods And Findings: We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink.
Arch Orthop Trauma Surg
January 2025
Department of Anaesthesia, Main-Kinzig-Kliniken, Herzbachweg 14, 63571, Gelnhausen, Germany.
Background: Total knee arthroplasty (TKA) is associated with moderate to severe postoperative pain. Pain control is crucial for rapid mobilisation and reduces side effects as well as the length of hospital stay. In this context, a variety of multimodal pain control regimes show good pain relief, including several nerve blocks, iPACK and local infiltration analgesia (LIA).
View Article and Find Full Text PDFCogn Res Princ Implic
January 2025
Department of Psychology and Centre for Integrative and Applied Neuroscience, York University, 4700 Keele St., Toronto, ON, M3J 1P3, Canada.
Developing ways to predict and encourage vaccine booster uptake are necessary for durable immunity responses. In a multi-nation sample, recruited in June-August 2021, we assessed delay discounting (one's tendency to choose smaller immediate rewards over larger future rewards), COVID-19 vaccination status, demographics, and distress level. Participants who reported being vaccinated were invited back one year later (n = 2547) to report their willingness to receive a booster dose, along with reasons for their decision.
View Article and Find Full Text PDFHernia
January 2025
Department of Minimally Invasive Surgery, National University Hospital, Bukit Timah, Singapore.
Background: Given the increasing prevalence of antiplatelet agent use and the lack of high-quality evidence, the CAPTAIN trial aimed to investigate the safety and provide recommendations on continuing acetylsalicylic acid perioperatively in patients undergoing elective laparoscopic totally extraperitoneal inguinal hernia repair (LIHR).
Methods: The CAPTAIN trial was a multicentre, surgeon blind, randomized controlled trial conducted from April 2016 to April 2023. Patients undergoing LIHR were eligible for inclusion.
Oncologist
January 2025
HonorHealth Research Institute, Scottsdale, AZ, United States.
Lessons Learned: Intravenous paricalcitol did not improve the efficacy of pembrolizumab, likely related to the short half-life.
Background: Immunotherapy has limited benefit in the treatment of advanced pancreatic cancer with the tumor microenvironment playing a key role in immune resistance. In preclinical studies, vitamin D receptor (VDR) agonists have been shown to sensitize pancreatic tumors to PD-1 blockade.
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