The dopamine D4 receptor (D4R) plays important roles in cognition, attention, and decision making. Novel D4R-selective ligands have promise in medication development for neuropsychiatric conditions, including Alzheimer’s disease and substance use disorders. To identify new D4R-selective ligands, and to understand the molecular determinants of agonist efficacy at D4R, we report a series of eighteen novel ligands based on the classical D4R agonist A-412997 (1, 2-(4-(pyridin-2-yl)piperidin-1-yl)-N-(m-tolyl)acetamide). Compounds were profiled using radioligand binding displacement assays, β-arrestin recruitment assays, cyclic AMP inhibition assays, and molecular dynamics computational modeling. We identified several novel D4R-selective (Ki ≤ 4.3 nM and >100-fold vs other D2-like receptors) compounds with diverse partial agonist and antagonist profiles, falling into three structural groups. These compounds highlight receptor–ligand interactions that control efficacy at D2-like receptors and may provide insights into targeted drug discovery, leading to a better understanding of the role of D4Rs in neuropsychiatric disorders.

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Health ICT is rapidly gaining popularity among policy makers and health consumers. Specific platforms for use in cancer care are missing. Aim: The aim of this pilot study was to: 1) test the feasibility, functionality and usability of a patient-led cancer care web platform: CanCare, in a sample of people undergoing cancer treatment and 2) ascertain if CanCare could enhance communication between patients, family, friends and health professionals. Methods: Cancer patients receiving chemotherapy were invited to participate. Data were collected via semi-structured interviews, online surveys and a website usage program. Results: Nine patients with four different types of cancer completed the study. All saw the potential of the website but many found it too complex to use, particularly when unwell post treatment. Many were frustrated by the lack of integration with existing hospital systems and the need to enter relevant data manually. The cancer-specific information tab rated highly and was used extensively. The website used alone did not promote interactions between family and/or health professionals. Conclusion: A patient-led cancer care website has the potential to help patients manage their cancer care but needs to be intuitive to use, integrated into hospital systems and requires significant family/carer and health professional engagement.