WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 326805
CAS#: 133865-89-1 (free base)
Description: Safinamide, also known as FCE-26743 and EMD-1195686, is a drug indicated for the treatment of Parkinson's disease with multiple methods of action. Potential additional uses might be restless legs syndrome (RLS) and epilepsy. Safinamide is a reversible and selective monoamine oxidase B inhibitor, reducing degradation of dopamine, and a glutamate release inhibitor. It also inhibits dopamine reuptake. Additionally, safinamide blocks sodium and calcium channels. Safinamide has been approved by the European Medicines Agency for the treatment of adult patients with idiopathic Parkinson’s disease as add-on therapy to a stable dose of Levodopa (L-dopa) alone or in combination with other PD drugs in patients with mid-to-late-stage fluctuating disease.
MedKoo Cat#: 326805
Name: Safinamide
CAS#: 133865-89-1 (free base)
Chemical Formula: C17H19FN2O2
Exact Mass: 302.1431
Molecular Weight: 302.35
Elemental Analysis: C, 67.53; H, 6.33; F, 6.28; N, 9.27; O, 10.58
Related CAS #: 133865-89-1 (free base) 202825-46-5 (mesylate)
Synonym: FCE-28073; FCE 28073; FCE28073; NW 1015; NW1015; NW-1015; PNU 151774E; PNU-151774E; EMD-1195686; EMD1195686; EMD 1195686; Safinamide, Xadago
IUPAC/Chemical Name: (S)-2-((4-((3-fluorobenzyl)oxy)benzyl)amino)propanamide
InChi Key: NEMGRZFTLSKBAP-LBPRGKRZSA-N
InChi Code: InChI=1S/C17H19FN2O2/c1-12(17(19)21)20-10-13-5-7-16(8-6-13)22-11-14-3-2-4-15(18)9-14/h2-9,12,20H,10-11H2,1H3,(H2,19,21)/t12-/m0/s1
SMILES Code: C[C@H](NCC1=CC=C(OCC2=CC=CC(F)=C2)C=C1)C(N)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Safinamide is a potent, selective, and reversible monoamine oxidase B (MAO-B) inhibitor (IC50=0.098 µM) over MAO-A (IC50=580 µM). |
| In vitro activity: | Using patch-clamp, it was shown that safinamide reversibly inhibited sodium currents in HEK293T cells transfected with hNav1.4. At the holding potential (hp) of -120 mV, the half-maximum inhibitory concentrations (IC50) were 160 and 33 μM at stimulation frequencies of 0.1 and 10 Hz, respectively. The calculated affinity constants of safinamide were dependent on channel state: 420 μM for closed channels and 9 μM for fast-inactivated channels. The p.F1586C mutation in hNav1.4 greatly impaired safinamide inhibition, suggesting that the drug binds to the local anesthetic receptor site in the channel pore. In a condition mimicking myotonia, i.e. hp. of -90 mV and 50-Hz stimulation, safinamide inhibited INa with an IC50 of 6 μM, being two-fold more potent than mexiletine. Using the two-intracellular microelectrodes current-clamp method, action potential firing was recorded in vitro in rat skeletal muscle fibers in presence of the chloride channel blocker, 9-anthracene carboxylic acid (9-AC), to increase excitability. Safinamide counteracted muscle fiber hyperexcitability with an IC50 of 13 μM. Reference: Exp Neurol. 2020 Jun;328:113287. https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(20)30118-7 |
| In vivo activity: | Safinamide (intraperitoneal injection; 90 mg/kg; once daily; 14 days) treatment prior to MCAO significantly ameliorates MCAO-caused cerebral infarction volume, neurological deficit, disruption of the brain-blood barrier (BBB), and impairs expression of tight junction protein occludin and ZO-1 in mice. Safinamide (intraperitoneal injection; 5 mg/kg, 15 mg/kg and 30 mg/kg) dose dependently inhibits the veratridine-induced GABA release and Glu release in vivo. At the dose 30 mg/kg, Safinamide prevents the effect of veratridine both on Glu (treatment F1,8=1.31; time×treatment interaction F8,64=2.4) and GABA (treatment F1,8=4.04; time F8,64=3.76, time×treatment interaction F8,64 = 2.83) release. Safinamide causes a slight, albeit not significant, reduction of veratridine-stimulated Glu release at 0.5 mg/kg and full inhibition at 5 and 15 mg/kg in rat Reference: J Pharmacol Exp Ther. 2018 Feb;364(2):198-206. https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=29167350 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 60.0 | 198.45 |
The following data is based on the product molecular weight 302.35 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| In vitro protocol: | 1. Desaphy JF, Farinato A, Altamura C, De Bellis M, Imbrici P, Tarantino N, Caccia C, Melloni E, Padoani G, Vailati S, Keywood C, Carratù MR, De Luca A, Conte D, Pierno S. Safinamide's potential in treating nondystrophic myotonias: Inhibition of skeletal muscle voltage-gated sodium channels and skeletal muscle hyperexcitability in vitro and in vivo. Exp Neurol. 2020 Jun;328:113287. doi: 10.1016/j.expneurol.2020.113287. Epub 2020 Mar 20. PMID: 32205118. |
| In vivo protocol: | 1. Morari M, Brugnoli A, Pisanò CA, Novello S, Caccia C, Melloni E, Padoani G, Vailati S, Sardina M. Safinamide Differentially Modulates In Vivo Glutamate and GABA Release in the Rat Hippocampus and Basal Ganglia. J Pharmacol Exp Ther. 2018 Feb;364(2):198-206. doi: 10.1124/jpet.117.245100. Epub 2017 Nov 22. PMID: 29167350. 2. Cruz MP. Xadago (Safinamide): A Monoamine Oxidase B Inhibitor for the Adjunct Treatment of Motor Symptoms in Parkinson's Disease. P T. 2017 Oct;42(10):622-637. PMID: 29018297; PMCID: PMC5614412. |
1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548819/ PubMed PMID: 31644126.
2: Safinamide for Parkinson's disease. Aust Prescr. 2019 Apr;42(2):78-79. doi: 10.18773/austprescr.2019.021. Epub 2018 Feb 28. Review. PubMed PMID: 31048946; PubMed Central PMCID: PMC6478961.
3: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK537993/ PubMed PMID: 30835405.
4: Bette S, Shpiner DS, Singer C, Moore H. Safinamide in the management of patients with Parkinson's disease not stabilized on levodopa: a review of the current clinical evidence. Ther Clin Risk Manag. 2018 Sep 18;14:1737-1745. doi: 10.2147/TCRM.S139545. eCollection 2018. Review. PubMed PMID: 30271159; PubMed Central PMCID: PMC6152599.
5: ▼ Safinamide for Parkinson's disease. Drug Ther Bull. 2018 May;56(5):54-57. doi: 10.1136/dtb.2018.5.0623. Review. PubMed PMID: 29760163.
6: Müller T. Safinamide: an add-on treatment for managing Parkinson's disease. Clin Pharmacol. 2018 Apr 5;10:31-41. doi: 10.2147/CPAA.S137740. eCollection 2018. Review. PubMed PMID: 29670409; PubMed Central PMCID: PMC5896660.
7: Teixeira FG, Gago MF, Marques P, Moreira PS, Magalhães R, Sousa N, Salgado AJ. Safinamide: a new hope for Parkinson's disease? Drug Discov Today. 2018 Mar;23(3):736-744. doi: 10.1016/j.drudis.2018.01.033. Epub 2018 Jan 12. Review. PubMed PMID: 29339106.
8: Baker DE, Kim AP. Formulary Drug Review: Safinamide. Hosp Pharm. 2017 Sep;52(8):532-543. doi: 10.1177/0018578717726046. Epub 2017 Aug 18. Review. PubMed PMID: 29276285; PubMed Central PMCID: PMC5735722.
9: Institute for Quality and Efficiency in Health Care. Safinamide: Benefit Assessment According to §35a Social Code Book V [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2015 Aug 13. Available from http://www.ncbi.nlm.nih.gov/books/NBK458393/ PubMed PMID: 29144651.
10: Institute for Quality and Efficiency in Health Care. Safinamide (Addendum to Commission A15-18) [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2015 Nov 5. Available from http://www.ncbi.nlm.nih.gov/books/NBK458416/ PubMed PMID: 29144646.
11: Müller T. Pharmacokinetic drug evaluation of safinamide mesylate for the treatment of mid-to-late stage Parkinson's disease. Expert Opin Drug Metab Toxicol. 2017 Jun;13(6):693-699. doi: 10.1080/17425255.2017.1329418. Review. PubMed PMID: 28537214.
12: deSouza RM, Schapira A. Safinamide for the treatment of Parkinson's disease. Expert Opin Pharmacother. 2017 Jun;18(9):937-943. doi: 10.1080/14656566.2017.1329819. Epub 2017 May 23. Review. PubMed PMID: 28504022.
13: Blair HA, Dhillon S. Safinamide: A Review in Parkinson's Disease. CNS Drugs. 2017 Feb;31(2):169-176. doi: 10.1007/s40263-017-0408-1. Review. PubMed PMID: 28110399.
14: Müller T, Foley P. Clinical Pharmacokinetics and Pharmacodynamics of Safinamide. Clin Pharmacokinet. 2017 Mar;56(3):251-261. doi: 10.1007/s40262-016-0449-5. Review. PubMed PMID: 27665574.
15: Müller T. Emerging approaches in Parkinson's disease - adjunctive role of safinamide. Ther Clin Risk Manag. 2016 Aug 2;12:1151-60. doi: 10.2147/TCRM.S86393. eCollection 2016. Review. PubMed PMID: 27536120; PubMed Central PMCID: PMC4977086.
16: Stocchi F, Torti M. Adjuvant therapies for Parkinson's disease: critical evaluation of safinamide. Drug Des Devel Ther. 2016 Feb 5;10:609-18. doi: 10.2147/DDDT.S77749. eCollection 2016. Review. PubMed PMID: 26917951; PubMed Central PMCID: PMC4751980.
17: Perez-Lloret S, Rascol O. The safety and efficacy of safinamide mesylate for the treatment of Parkinson's disease. Expert Rev Neurother. 2016;16(3):245-58. doi: 10.1586/14737175.2016.1150783. Epub 2016 Feb 19. Review. PubMed PMID: 26849427.
18: Müller T. Safinamide for symptoms of Parkinson's disease. Drugs Today (Barc). 2015 Nov;51(11):653-9. doi: 10.1358/dot.2015.51.11.2414529. Review. PubMed PMID: 26744740.
19: Fabbri M, Rosa MM, Abreu D, Ferreira JJ. Clinical pharmacology review of safinamide for the treatment of Parkinson's disease. Neurodegener Dis Manag. 2015 Dec;5(6):481-96. doi: 10.2217/nmt.15.46. Epub 2015 Nov 20. Review. PubMed PMID: 26587996.
20: Deeks ED. Safinamide: first global approval. Drugs. 2015 Apr;75(6):705-11. doi: 10.1007/s40265-015-0389-7. Review. PubMed PMID: 25851099.
