Browsing by Subject "Agonist"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Patient considerations in the management of chronic constipation: focus on prucalopride
    (Dove Press, 2016-07-28) Shim, Andrea; Department of Medicine, IU School of Medicine
    Chronic constipation is a common condition that significantly impacts health care utilization, productivity, and quality of life. Laxatives are commonly used, although often insufficient in restoring normal bowel function or providing adequate relief. There remains a significant need for the development of novel agents to optimize treatment of this condition. This review provides an overview of the preclinical and clinical trial data, supporting the efficacy and safety of prucalopride, a highly selective 5-HT4 receptor agonist that has been approved by the European Medicine Agency for the treatment of chronic constipation in adults who have failed standard laxative therapy. Unlike older 5-HT4 agonists, prucalopride has not been associated with adverse cardiovascular side effects or QT prolongation owing to its high selectivity and affinity for the 5-HT4 receptor without clinically significant cross-reactivity at the human ether-à-go-go-related gene (hERG) potassium channel or 5-HT receptor subtypes that have previously been implicated in adverse cardiovascular events and arrhythmias. Careful safety assessments have documented the relative safety and tolerability of this agent in various patient groups. Focus has also been placed on demonstrating efficacy with regard to bowel function, symptoms, and patient-reported outcomes such as the Patient Assessment of Constipation-Symptoms and the Patient Assessment of Constipation Quality of Life scores to support the use of prucalopride as a safe and effective therapeutic option for the management of chronic constipation.
  • Thumbnail Image
    Item
    Suppression of osteoclastogenesis via α2-adrenergic receptors
    (Spandidos Publications, 2018-05) Hamajima, Kosuke; Hamamura, Kazunori; Chen, Andy; Yokota, Hiroki; Mori, Hironori; Yo, Shoyoku; Kondo, Hisataka; Tanaka, Kenjiro; Ishizuka, Kyoko; Kodama, Daisuke; Hirai, Takao; Miyazawa, Ken; Goto, Shigemi; Togari, Akifumi; Biomedical Engineering, School of Engineering and Technology
    The sympathetic nervous system is known to regulate osteoclast development. However, the involvement of α2-adrenergic receptors (α2-ARs) in osteoclastogenesis is not well understood. In the present study, their potential role in osteoclastogenesis was investigated. Guanabenz, clonidine and xylazine were used as agonists of α2-ARs, while yohimbine and idazoxan were employed as antagonists. Using RAW264.7 pre-osteoclast and primary bone marrow cells, the mRNA expression of the osteoclast-related genes nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K was evaluated following induction with receptor activator of nuclear factor κB ligand (RANKL). TRAP staining was also conducted to assess effects on osteoclastogenesis in mouse bone marrow cells in vitro. Administration of 5-20 µM guanabenz (P<0.01, for RANKL-only treatment), 20 µM clonidine (P<0.05, for RANKL-only treatment) and 20 µM xylazine (P<0.05, for RANKL-only treatment) attenuated RANKL-induced upregulation of NFATc1, TRAP and cathepsin K mRNA. Furthermore, the reductions in these mRNAs by 10 µM guanabenz and 20 µM clonidine in the presence of RANKL were attenuated by 20 µM yohimbine or idazoxan (P<0.05). The administration of 5-20 µM guanabenz (P<0.01, for RANKL-only treatment) and 10-20 µM clonidine (P<0.05, for RANKL-only treatment) also decreased the number of TRAP-positive multi-nucleated osteoclasts. Collectively, the present study demonstrates that α2-ARs may be involved in the regulation of osteoclastogenesis.