Efficacy and safety of high doses of safinamide in advanced Parkinson disease

Rodríguez‐Jorge, Fernando; Beltrán, Álvaro; Chico, Juan Luis; Parra, Paloma; Baena-Álvarez, Belén; Pagonabarraga, Javier; Pérez-Torre, Paula; Pareés, Isabel; López-Sendón, J.L.; Martínez‐Castrillo, Juan Carlos; Alonso‐Cánovas, Araceli

doi:10.1016/j.parkreldis.2022.03.010

Cited by 2 publications

(1 citation statement)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding the inhibitory effect of SAF on MAO-B, SAF may lyse and remove the components of the surface membrane of various host cells (Edmondson and Binda, 2018), thus accessing cytosolic or mitochondrial enzymes. Thus, the stimulatory perturbation of I Na [ I Na(T) , I Na(L) , I Na(W) , and I Na(P) ] is clinically achievable by using SAF and may have pharmacological, therapeutic, and toxicological relevance in humans [ 12 , 16 , 17 ].…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

Switching from Rasagiline to Safinamide as an Add-On Therapy Regimen in Patients with Levodopa: A Literature Review

et al. 2023

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a complex disease, and the treatment is focused on the patient’s clinical symptoms. Levodopa continues to be the most effective drug for symptomatic PD treatment. However, chronic levodopa treatment is associated with the development of motor complications in most patients. Add-on therapeutic drugs, such as dopamine agonists and monoamine oxidase B (MAO-B) inhibitors, for example, safinamide and rasagiline, may be a desirable addition to continuously increase the levodopa dose for the optimization of motor control in PD. The scientific literature shows that safinamide significantly alleviated motor fluctuations with no increase in troublesome dyskinesia, thanks to its unique double mechanism, providing further benefits to fluctuating PD patients when compared to a placebo or other drugs. Switching from rasagiline to safinamide has been shown to improve the wearing-off phenomena, which is defined as the recurrent, predictable worsening of symptoms of parkinsonism at the end of the levodopa dose until the next dose reaches a clinical effect. In this situation, safinamide may be helpful for reducing the total daily dose of levodopa, improving the OFF time and ON time without troublesome dyskinesias, and being more effective than other MAO-B inhibitors. In this narrative review, we explore the switch from rasagiline to safinamide in patients with motor complications as a feasible and effective alternative to optimize antiparkinsonian treatment.

show abstract

Efficacy and safety of high doses of safinamide in advanced Parkinson disease

Cited by 2 publications

References 4 publications

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

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

Switching from Rasagiline to Safinamide as an Add-On Therapy Regimen in Patients with Levodopa: A Literature Review

Contact Info

Product

Resources

About