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.
Toward the identification of neuroprotective agents : g-scale synthesis, pharmacokinetic evaluation and CNS distribution of (R)-RC-33, a promising Sigma1 receptor agonist / A. Marra, D. Rossi, L. Pignataro, C. Bigogno, A. Canta, N. Oggioni, A. Malacrida, M. Corbo, G. Cavaletti, M. Peviani, D. Curti, G. Dondio, S. Collina. - In: FUTURE MEDICINAL CHEMISTRY. - ISSN 1756-8919. - 8:3(2016 Mar), pp. 287-295. [10.4155/fmc.15.191]
Toward the identification of neuroprotective agents : g-scale synthesis, pharmacokinetic evaluation and CNS distribution of (R)-RC-33, a promising Sigma1 receptor agonist
L. Pignataro;
2016
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.File | Dimensione | Formato | |
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