Journal: Acta pharmacologica Sinica

Article Title: Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain.

doi: 10.1038/s41401-021-00682-9

Figure Lengend Snippet: Fig. 1 Concentration-dependent inhibition of Nav1.7 currents expressed in HEK293 cells by compound QLS-81. a Chemical structure of QLS-81: (S)-2-((3-(4-((2-fluorobenzyl) oxy) phenyl) propyl) amino) propanamide and ralfinamide. b Left panel, top, Nav1.7 currents stably expressed in HEK293 cells held at −130 mV were elicited by a double-pulse protocol consisting of a conditional pulse at 0 mV (15 ms) for channel activation and a test pulse at 0 mV (15 ms) for 50% channel inactivation. Left panel, bottom, representative current traces elicited by the second test pulse before and after application of QLS-81. The dashed line represents zero-current levels. Right panel, summary for normalized inhibition of activated and inactivated Nav1.7 currents by QLS-81. Paired t-test, ***P < 0.001, n = 10. c Inhibition of representative Nav1.7 current traces elicited by the test pulse (panel (b)) before and after QLS-81 (left panel) and ralfinamide (middle panel) at different concentrations. The dashed line represents zero-current levels. Right panel, curves were fitted using a logistic function for concentration- dependent inhibition of Nav1.7 by QLS-81 (black) with IC50 of 3.5 ± 1.5 μM (n = 3–11) and ralfinamide (red) with IC50 of 37.1 ± 2.9 μM (n = 5–8). d Representative current traces of Nav1.4 (left panel) and Nav1.5 (middle panel) elicited by the depolarizing potential at 0 mV (test pulse of a panel (b)) before and after different concentrations of QLS-81. The dashed line represents zero-current levels. Right panel, curves were fitted using the logistic function for concentration-dependent inhibition of Nav1.4 with IC50 of 37.3 ± 7.3 μM (n = 5) and Nav1.5 with 15.4 ± 1.6 μM (n = 5–8) by QLS-81. All data were expressed as the mean ± SEM.

Article Snippet: Ralfinamide was purchased from MedChemExpress LLC.

Techniques: Concentration Assay, Inhibition, Stable Transfection, Activation Assay

Journal: Acta pharmacologica Sinica

Article Title: Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain.

doi: 10.1038/s41401-021-00682-9

Figure Lengend Snippet: Fig. 5 Antinociceptive effects of QLS-81 on pain induced by spinal nerve injury (SNI) and inflammation in mice. a Top panel, a schematic time-course of paw mechanical withdrawal threshold (PMWT) measured by von Frey hair stimulation in a mouse model of SNI. Bottom panel, dose-dependent antinociception by QLS-81 (2, 5, and 10 mg/kg, i.p.), morphine (5 mg/kg), and ralfinamide (10 mg/kg) in SNI model. Two-way ANOVA followed by Bonferroni post hoc tests revealed a significant decrease of PMWT between-group sham and group vehicle, ***P < 0.001; a significant increase of PMWT in QLS-81 (2, 5, 10 mg/kg, i.p.) injected groups, compared with group vehicle, ##P < 0.01, ###P < 0.001; and also a significant difference between group QLS-81 (10 mg/kg) and group ralfinamide (10 mg/kg), $$$P < 0.001. All data were expressed as the mean ± SEM, n = 10–12. b Top panel, experimental design, and schedule for formalin test in a mouse model of inflammatory pain. Bottom panels, formalin-induced spontaneous pain behavior was divided into two phases and analyzed following subcutaneous (sc.) injection of formalin. QLS-81 (5, 10, and 20 mg/kg) dose-dependently attenuated the nocifensive behaviors induced by formalin at phase II (right) but not at phase I. One-way ANOVA followed by Tukey test, *P < 0.01 and ***P < 0.001 vs. vehicle, n = 10–12. All data were expressed as the mean ± SEM.

Article Snippet: Ralfinamide was purchased from MedChemExpress LLC.

Techniques: Injection

Journal: Molecules

Article Title: Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

doi: 10.3390/molecules21070793

Figure Lengend Snippet: Chemical structures of ralfinamide and safinamide.

Article Snippet: Ralfinamide is an orally active selective blocker of the VGSC, Nav1.7, and has been developed by Newron Pharmaceuticals [ ].

Techniques:

Journal: Molecules

Article Title: Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

doi: 10.3390/molecules21070793

Figure Lengend Snippet: In vivo activity of the synthesized compounds in the formalin test performed.

Article Snippet: Ralfinamide is an orally active selective blocker of the VGSC, Nav1.7, and has been developed by Newron Pharmaceuticals [ ].

Techniques: In Vivo, Activity Assay, Synthesized

Journal: Molecules

Article Title: Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

doi: 10.3390/molecules21070793

Figure Lengend Snippet: Cumulative duration of licking time of injected paw following oral ( a ) and i.p. ( b ) administration of ralfinamide (ral) and compound 6a during the formalin test. Significant differences between vehicle and drug-treated groups were evaluated by the Dunnett’s test. * p < 0.05.

Article Snippet: Ralfinamide is an orally active selective blocker of the VGSC, Nav1.7, and has been developed by Newron Pharmaceuticals [ ].

Techniques: Injection

Journal: Molecules

Article Title: Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

doi: 10.3390/molecules21070793

Figure Lengend Snippet: Inhibitory activities of select compounds on the tetrodotoxin-sensitive and inactivated Nav1.7.

Article Snippet: Ralfinamide is an orally active selective blocker of the VGSC, Nav1.7, and has been developed by Newron Pharmaceuticals [ ].

Techniques: Inhibition