New salts of teriflunomide (TFM) – Single crystal X-ray and solid state NMR investigation

Pawlak, T.; Paluch, Piotr; Dolot, Rafał; Bujacz, G.; Potrzebowski, Marek J.

doi:10.1016/j.ssnmr.2022.101820

Cited by 1 publication

(1 citation statement)

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“…SAF engages in hydrophobic interactions with certain amino acid residues, such as Phe 103, Val 106, Arg 120, Asp 123, Arg 127, Thr 479, and Glu 483. In addition to interacting with intramolecular hydrogen bonds [ 58 ], SAF forms three hydrogen bonds with the Na V -channel residues Pro 104, His 115, and Trp 119, with the bond lengths being 2.81, 3.16, and 2.90 Å, respectively. The binding affinity for the interaction between SAF and MAO-B is –7.8 kcal/mol, and the upper and lower root-mean-square deviations (RMSD) in atomic positions were 49.76 and 60.68, respectively.…”

Section: Resultsmentioning

confidence: 99%

Safinamide, an inhibitor of monoamine oxidase, modulates the magnitude, gating, and hysteresis of sodium ion current

Hung,

Wu,

Huang

2024

BMC Pharmacol Toxicol

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Background Safinamide (SAF), an α-aminoamide derivative and a selective, reversible monoamine oxidase (MAO)-B inhibitor, has both dopaminergic and nondopaminergic (glutamatergic) properties. Several studies have explored the potential of SAF against various neurological disorders; however, to what extent SAF modulates the magnitude, gating, and voltage-dependent hysteresis [Hys(V)] of ionic currents remains unknown. Methods With the aid of patch-clamp technology, we investigated the effects of SAF on voltage-gated sodium ion (NaV) channels in pituitary GH3 cells. Results SAF concentration-dependently stimulated the transient (peak) and late (sustained) components of voltage-gated sodium ion current (INa) in pituitary GH3 cells. The conductance–voltage relationship of transient INa [INa(T)] was shifted to more negative potentials with the SAF presence; however, the steady-state inactivation curve of INa(T) was shifted in a rightward direction in its existence. SAF increased the decaying time constant of INa(T) induced by a train of depolarizing stimuli. Notably, subsequent addition of ranolazine or mirogabalin reversed the SAF-induced increase in the decaying time constant. SAF also increased the magnitude of window INa induced by an ascending ramp voltage Vramp. Furthermore, SAF enhanced the Hys(V) behavior of persistent INa induced by an upright isosceles-triangular Vramp. Single-channel cell-attached recordings indicated SAF effectively increased the open-state probability of NaV channels. Molecular docking revealed SAF interacts with both MAO and NaV channels. Conclusion SAF may interact directly with NaV channels in pituitary neuroendocrine cells, modulating membrane excitability.

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Section: Resultsmentioning

confidence: 99%