Background: Prucalopride is a selective serotonin type 4 (5-HT) receptor agonist indicated for treatment of chronic idiopathic constipation (CIC) in adults (2 mg orally, daily). 5-HT receptors are present in the central nervous system; therefore, non-clinical and clinical assessments were performed to evaluate the tissue distribution and abuse potential of prucalopride.
Methods: In vitro receptor-ligand binding studies were performed to assess the affinity of prucalopride (≤1 mM) for peptide receptors, ion channels, monoamine neurotransmitters and 5-HT receptors. The tissue distribution of C-prucalopride (5 mg base-equivalent/kg) was investigated in rats. Behavioural assessments in mice, rats and dogs after treatment with single or repeated (up to 24 months) subcutaneous or oral doses of prucalopride (0.02-640 mg/kg across species) were performed. Treatment-emergent adverse events possibly indicative of abuse potential during prucalopride CIC clinical trials were evaluated.
Results: Prucalopride showed no appreciable affinity for the receptors and ion channels investigated; its affinity (at ≤100 μM) for other 5-HT receptors was 150-10,000 times lower than that for the 5-HT receptor. In rats, <0.1% of the administered dose was found in the brain and concentrations were below the limit of detection within 24 hours. At supratherapeutic doses (≥20 mg/kg), mice and rats exhibited palpebral ptosis, and dogs exhibited salivation, eyelid tremors, decubitis, pedalling movements and sedation. All clinical treatment-emergent adverse events, possibly indicative of abuse potential, except dizziness, occurred in <1% of patients treated with prucalopride or placebo.
Conclusion: This series of non-clinical and clinical studies suggest low abuse potential for prucalopride.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983627 | PMC |
http://dx.doi.org/10.7573/dic.2022-6-1 | DOI Listing |
Virol J
January 2025
Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518118, China.
Background: SHEN26 (ATV014) is an oral RNA-dependent RNA polymerase (RdRp) inhibitor with potential anti-SARS-CoV-2 activity. Safety, tolerability, and pharmacokinetic characteristics were verified in a Phase I study. This phase II study aimed to verify the efficacy and safety of SHEN26 in COVID-19 patients.
View Article and Find Full Text PDFAnn Biomed Eng
January 2025
School of Mechanical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Purpose: To evaluate the mechanical wear of cartilage with different types of degradation.
Methods: Bovine osteochondral explants were treated with interleukin-1β (IL-1β) to mimic inflammatory conditions, with chondroitinase ABC (ChABC) to specifically remove glycosaminoglycans (GAGs), or with collagenase to degrade the collagen network during 5 days of culture. Viscoelastic properties of cartilage were characterized via indentation.
Chin J Traumatol
January 2025
Department of Emergency Surgery and Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China. Electronic address:
Purpose: The fixation method commonly employed worldwide for treating unstable fractures of the posterior pelvic ring is the percutaneous iliosacral screw technique. However, prolonged operation time and frequent fluoroscopies result in surgical risks. This study aimed to investigate whether a new triangulation method could reduce operative and fluoroscopy times and increase the accuracy of screw placement.
View Article and Find Full Text PDFMethods Cell Biol
January 2025
T Cell Lymphoma Group, Josep Carreras Leukaemia Research Institute, Barcelona, Spain. Electronic address:
T cell lymphoma constitutes a complex group of diseases, characterized by heterogeneous molecular features and clinical symptoms, and a dismal outcome no matter the therapeutic strategy chosen. In an attempt to improve patients' survival chances, treatment combinations (chemotherapy, radiotherapy, immunotherapy, gene therapy and thermotherapy) have been tested for their synergistic effects that may dramatically improve outcomes and reduce the side effects of each single modality treatment when therapeutic effects add up while side effects are distributed. In this context, nanoscale drug delivery agents have been developed and exploited to enhance the release of drugs in the treatment of several diseases, showing potential benefits in terms of pharmaceutical flexibility, selectivity, dose reduction and minimization of adverse effects.
View Article and Find Full Text PDFJ Shoulder Elbow Surg
January 2025
Department of Orthopedic surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:
Background: Heterotopic ossification (HO) involves abnormal bone formation in soft tissues near joints, commonly occurring after elbow trauma or surgery, leading to pain and functional limitations. Previous studies have primarily characterized HO distribution based on bony landmarks, lacking a detailed investigation into the characteristics of its distribution in periarticular soft tissue in post-traumatic elbows. This study aimed to (1) develop a muscle-guided classification system using computed tomography (CT) to map HO relative to elbow muscle-tendon units and (2) investigate correlations between HO location and severity.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!