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.

Marra, A., Rossi, D., Pignataro, L., Bigogno, C., Canta, A., Oggioni, N., et al. (2016). Toward the identification of neuroprotective agents: G-scale synthesis, pharmacokinetic evaluation and CNS distribution of (R)-RC-33, a promising SIGMA1 receptor agonist. FUTURE MEDICINAL CHEMISTRY, 8(3), 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

CANTA, ANNALISA ROSANNA;OGGIONI, NORBERTO;MALACRIDA, ALESSIO;CAVALETTI, GUIDO ANGELO;
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.
Articolo in rivista - Articolo scientifico
amyotrophic lateral sclerosis; CNS distribution; multiple sclerosis; neurological disorders; Parkinson's disease; pharmacokinetic profile; S1R agonist;
amyotrophic lateral sclerosis; CNS distribution; multiple sclerosis; neurological disorders; Parkinson's disease; pharmacokinetic profile; S1R agonist; Drug Discovery3003 Pharmaceutical Science; Pharmacology; Molecular Medicine
English
2016
8
3
287
295
none
Marra, A., Rossi, D., Pignataro, L., Bigogno, C., Canta, A., Oggioni, N., et al. (2016). Toward the identification of neuroprotective agents: G-scale synthesis, pharmacokinetic evaluation and CNS distribution of (R)-RC-33, a promising SIGMA1 receptor agonist. FUTURE MEDICINAL CHEMISTRY, 8(3), 287-295 [10.4155/fmc.15.191].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/111070
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