Adenosine A1 receptor (A1R) agonists as anti-lipolytic agents and enhancers of tissue insulin sensitivity could be useful in the treatment of metabolic disorders but their use is limited by unwanted cardiac effects and tachyphylaxis. Partial A1R agonists can overcome these problems, while maintaining significant anti-lipolytic effects due to greater A1R reserve in the adipose tissue.
Based on preliminary data, this research, carried out either in in vitro (human and rat adipocytes, adipose stem cell, isolated heart and vessels) or in vivo models (healthy, diabetic, diabetic-obese rats), will study a new adenosine derivative with chemical features different from previous partial A1R agonists, good affinity and selectivity at human A1R, that could show antilipolytic/antidiabetic and also anti-adipogenic activities and less ability to cause cardiovascular side-effects and receptor desensitization. This evidence would be crucial for its use in chronic treatment of metabolic syndromes.
Researchers involved in this project, submitted for a grant to the Italian Minister of Health:
Stefano Martinotti, Professor of Clinical Pathology, Department of Experimental and Clinical Sciences, University of Chieti. Italy
Renata Ciccarelli, Professor of Pharmacology, Department of Experimental and Clinical Sciences, University of Chieti. Italy
Rosaria Volpini, Professor of Medicinal Chemistry, Department of Pharmacy, University of Camerino.
Based on preliminary data, this research, carried out either in in vitro (human and rat adipocytes, adipose stem cell, isolated heart and vessels) or in vivo models (healthy, diabetic, diabetic-obese rats), will study a new adenosine derivative with chemical features different from previous partial A1R agonists, good affinity and selectivity at human A1R, that could show antilipolytic/antidiabetic and also anti-adipogenic activities and less ability to cause cardiovascular side-effects and receptor desensitization. This evidence would be crucial for its use in chronic treatment of metabolic syndromes.
Researchers involved in this project, submitted for a grant to the Italian Minister of Health:
Stefano Martinotti, Professor of Clinical Pathology, Department of Experimental and Clinical Sciences, University of Chieti. Italy
Renata Ciccarelli, Professor of Pharmacology, Department of Experimental and Clinical Sciences, University of Chieti. Italy
Rosaria Volpini, Professor of Medicinal Chemistry, Department of Pharmacy, University of Camerino.