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Purity: ≥98%
Safinamide (formerly known as EMD-1195686; FCE-26743; EMD1195686; FCE26743; trade name: Xadago) is an FDA approved anti-PD ( Parkinson's disease) drug. It acts by selectively and reversibly inhibiting MAO-B with an IC50 of 98 nM, and exhibits 5918-fold selectivity against MAO-A. In addition, Safinamide is voltage-dependent sodium and calcium channel blocker. It appears to bind to the batrachotoxin-sensitive site 2 of the voltage-sensitive sodium channels. In 2017, FDA approved Safinamide to treat Parkinson's disease. Safinamide blocks N and L-type calcium channels and inhibits glutamate and aspartate release from synaptic terminals.
| ln Vitro |
Peak sodium current amplitude is lowered by safinamide (1–300 µM) in a concentration-dependent manner. The IC50 value was 262 µM when currents were driven to a Vtest of +10 mV from a Vh of -110 mV. In rat cortical neurons, safinamide exhibits an inhibitory action with a reduced IC50 value (8 µM) when the holding potential is depolarized to -53 mV[1].
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| ln Vivo |
When administered intraperitoneally (90 mg/kg, once daily for 14 days), safinamide significantly reduces the volume of cerebral infarction caused by MCAO in mice, as well as the neurological deficit, disruption of the blood-brain barrier (BBB), and expression of the tight junction proteins occludin and ZO-1[3]. In vivo, veratridine-induced GABA and Glu release is dose-dependently inhibited by safinamide (intraperitoneal injection; 5 mg/kg, 15 mg/kg, and 30 mg/kg). Safinamide blocks the effects of veratridine on GABA (treatment F1,8=4.04; time F8,64=3.76, time× treatment interaction F8,64 = 2.83) and Glu (treatment F1,8=1.31; time× treatment interaction F8,64=2.4) release at a dose of 30 mg/kg. In rats, safinamide completely inhibits veratridine-stimulated Glu release at doses of 5 and 15 mg/kg and reduces it slightly, but not significantly[3].
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| Animal Protocol |
Animal/Disease Models: Focal cerebral ischemia C57/BL6 male mouse Model[3]
Doses: 90 mg/kg Route of Administration: intraperitoneal (ip)injection; one time/day; 14 days Experimental Results: Dramatically diminished infarction volume in brain areas. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Rapid with peak plasma concentrations ranging from 2 to 4 h, total bioavailability is 95%. Food prolonged the rate and did not affect the extent of absorption of safinamide. 76% renal, 1.5% faeces 1.8 litres/kg total oral clearance of plasma , which accounts for parent safinamide as well as metabolites, was on average only 17.53 ± 2.71 ml/h × kg Metabolism / Metabolites The principal step is mediated by amidases which have not been identified, and produces safinamide acid. It is also metabolized to O-debenzylated safinamide and N-delkylated amine. The N-dealkylated amine is then oxidized to a carboxylic acid and finally glucuronidated. Dealkylation reactions are mediated by cytochrome P450s (CYPs), especially CYP3A4. Safinamide acid binds to organic anion transporter 3 (OAT3), but no clinical relevance of this interaction has been determined. Safinamide also binds to ABCG2 transiently. No other transporter affinities have been found in preliminary studies. Biological Half-Life 22 h |
| Toxicity/Toxicokinetics |
Hepatotoxicity
Safinamide has been reported to cause serum enzyme elevations in a small proportion of patients treated long term, although the abnormalities were usually mild and self-limiting and were usually no more frequent than with placebo or comparator agents. Safinamide has not been implicated in cases of acute liver injury, but such instances have been reported with nonspecific MAO inhibitors. Likelihood score: E (unlikely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of safinamide during breastfeeding. Because of liver toxicity in nursing rat pups, the manufacturer recommends that the drug not be used in nursing mothers. Alternate agents are preferred. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding 88–90% |
| References |
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| Additional Infomation |
Safinamide is an amino acid amide.
Safinamide is for the treatment of parkinson's disease. It was approved in Europe in February 2015, and in the United States on March 21, 2017. Safinamide is a Monoamine Oxidase Type B Inhibitor. The mechanism of action of safinamide is as a Monoamine Oxidase-B Inhibitor, and Breast Cancer Resistance Protein Inhibitor. Safinamide is an inhibitor of monoamine oxidase used as adjunctive therapy in combination with levodopa and carbidopa in the management of Parkinson’s disease. Safinamide has been associated with a low rate of serum enzyme elevations during treatment, but has not been linked to instances of clinically apparent acute liver injury. See also: Safinamide Mesylate (active moiety of). Drug Indication Safinamide is indicated as an add-on treatment to levodopa with or without other medicines for Parkinson’s disease Xadago is indicated for the treatment of adult patients with idiopathic Parkinson's disease (PD) as add-on therapy to a stable dose of Levodopa (L-dopa) alone or in combination with other PD medicinal products in mid-to late-stage fluctuating patients. Mechanism of Action Safinamide is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. |
| Molecular Formula |
C17H19FN2O2
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|---|---|
| Molecular Weight |
302.34
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| Exact Mass |
302.143
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| CAS # |
133865-89-1
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| Related CAS # |
Safinamide mesylate;202825-46-5;Safinamide-d4-1;2748522-33-8
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| PubChem CID |
131682
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
476.7±40.0 °C at 760 mmHg
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| Melting Point |
208-212°
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| Flash Point |
242.1±27.3 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.570
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| LogP |
2.37
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
22
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| Complexity |
346
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H](C(=O)N)NCC1=CC=C(C=C1)OCC2=CC(=CC=C2)F
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| InChi Key |
NEMGRZFTLSKBAP-LBPRGKRZSA-N
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| 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
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| Chemical Name |
(S)-2-((4-((3-fluorobenzyl)oxy)benzyl)amino)propanamide
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| Synonyms |
PNU-151774E,FCE28073; EMD-1195686; EMD 1195686; FCE-26743; FCE 26743; FCE26743; EMD1195686; Safinamide. trade name: Xadago
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3075 mL | 16.5377 mL | 33.0753 mL | |
| 5 mM | 0.6615 mL | 3.3075 mL | 6.6151 mL | |
| 10 mM | 0.3308 mL | 1.6538 mL | 3.3075 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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