Annamaria Marra1, Daniela Rossi1, Luca Pignataro2, Chiara Bigogno3, Annalisa Canta4, Norberto Oggioni4, Alessio Malacrida4, Massimo Corbo5, Guido Cavaletti4, Marco Peviani6, Daniela Curti6, Giulio Dondio3, Simona Collina1. 1. Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia-I, Italy. 2. Università degli Studi di Milano, Dipartimento di Chimica, Via C. Golgi 19, 20133 Milano-I, Italy. 3. Aphad S.r.l., Via della Resistenza 65, 20090 Buccinasco Milan-I, Italy. 4. Experimental Neurology Unit, Department of Surgery & Translational Medicine & Milan Center for Neuroscience, University of Milan Bicocca, Via Cadore 48, 20900 Monza-I, Italy. 5. Department of Neurorehabilitation Sciences, Casa Cura Policlinico (CCP), via Dezza 48, 20144 Milan-I, Italy. 6. Department of Biology & Biotechnology "L. Spallanzani", University of Pavia, Via Ferrata 9, 27100 Pavia-I, Italy.
Abstract
AIM: Nowadays, there is a great interest in the therapeutic potential of sigma1 receptor ligands for treating different CNS pathologies. Our previous investigations led to identify (R)-RC-33 as a potent and selective S1R agonist. RESULTS: Herein, we report the gram-scale synthesis, pharmacokinetic profile and CNS distribution of (R)-RC-33 in the mouse to determine the most suitable dosage schedule for in vivo administration. For comparative purposes, the same experiments were also performed with PRE-084, the most widely used S1R agonist commonly in pharmacological experiments. DISCUSSION: (R)-RC-33 shows a similar pharmacokinetic profile and a better CNS distribution when compared with PRE-084. CONCLUSION: (R)-RC-33 may be a promising candidate for in vivo studies in animal models of neurodegenerative diseases.
AIM: Nowadays, there is a great interest in the therapeutic potential of sigma1 receptor ligands for treating different CNS pathologies. Our previous investigations led to identify (R)-RC-33 as a potent and selective S1R agonist. RESULTS: Herein, we report the gram-scale synthesis, pharmacokinetic profile and CNS distribution of (R)-RC-33 in the mouse to determine the most suitable dosage schedule for in vivo administration. For comparative purposes, the same experiments were also performed with PRE-084, the most widely used S1R agonist commonly in pharmacological experiments. DISCUSSION: (R)-RC-33 shows a similar pharmacokinetic profile and a better CNS distribution when compared with PRE-084. CONCLUSION:(R)-RC-33 may be a promising candidate for in vivo studies in animal models of neurodegenerative diseases.
Authors: Serena Della Volpe; Roberta Listro; Michela Parafioriti; Marcello Di Giacomo; Daniela Rossi; Francesca Alessandra Ambrosio; Giosuè Costa; Stefano Alcaro; Francesco Ortuso; Anna K H Hirsch; Francesca Vasile; Simona Collina Journal: ACS Med Chem Lett Date: 2020-01-28 Impact factor: 4.345