Identification
- Summary
Safinamide is a MAO-B inhibitor used as an add-on treatment to levodopa/carbidopa for Parkinson's disease during "off" episodes.
- Brand Names
- Xadago
- Generic Name
- Safinamide
- DrugBank Accession Number
- DB06654
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Safinamide (DB06654)
- Weight
- Average: 302.349
Monoisotopic: 302.143056023 - Chemical Formula
- C17H19FN2O2
- Synonyms
- Safinamida
- Safinamide
- External IDs
- EMD 1195686
- EMD-1195686
Pharmacology
- Indication
Safinamide is indicated as an add-on treatment to levodopa with or without other medicines for Parkinson’s disease
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in management of Parkinson's disease •••••••••••• - Contraindications & Blackbox Warnings
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Not Available
- 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.
Target Actions Organism AAmine oxidase [flavin-containing] B antagonistHumans - Absorption
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.
- Volume of distribution
1.8 litres/kg
- Protein binding
88–90%
- Metabolism
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.
- Route of elimination
76% renal, 1.5% faeces
- Half-life
22 h
- Clearance
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
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
uncontrolled involuntary movement, falls, nausea, and trouble sleeping or falling asleep (insomnia) Patients who have an overdose may experience hypertension (high blood pressure), orthostatic hypotension, hallucinations, psychomotor agitation, nausea, vomiting, and dyskinesia.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Safinamide is combined with 1,2-Benzodiazepine. Abaloparatide Safinamide may increase the orthostatic hypotensive activities of Abaloparatide. Abametapir The serum concentration of Safinamide can be increased when it is combined with Abametapir. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Safinamide is combined with Abciximab. Abemaciclib Safinamide may decrease the excretion rate of Abemaciclib which could result in a higher serum level. - Food Interactions
- Avoid excessive or chronic alcohol consumption. Ingesting alcohol may increase the sedative effects of safinamide.
- Avoid St. John's Wort. This herb may increase the risk of serotonin syndrome, and therefore, concomitant use is contraindicated.
- Avoid tyramine-containing foods and supplements. Avoid foods containing high amounts of tyramine (>150mg) as these foods may cause a significant elevation in blood pressure. Tyramine-containing foods include cheese, red wine, fava beans, pickled food, cured food, and alcoholic beverages.
- Take at the same time every day.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Safinamide mesylate YS90V3DTX0 202825-46-5 YKOCHIUQOBQIAC-YDALLXLXSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Onstryv Tablet 100 mg Oral Valeo Pharma Corp. 2019-07-08 Not applicable Canada 
Onstryv Tablet 50 mg Oral Valeo Pharma Corp. 2019-07-08 Not applicable Canada Xadago Tablet, film coated 100 mg Oral Zambon Sp A 2021-01-27 Not applicable EU 
Xadago Tablet, film coated 50 mg Oral Zambon Sp A 2021-01-27 Not applicable EU Xadago Tablet, film coated 100 mg/1 Oral MDD US Operations LLC, a subsidiary of Supernus Pharmaceuticals, Inc. 2017-05-08 Not applicable US 
Categories
- ATC Codes
- N04BD03 — Safinamide
- Drug Categories
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Amines
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Anti-Parkinson Drugs
- Antidepressive Agents
- BCRP/ABCG2 Inhibitors
- Benzene Derivatives
- Benzyl Compounds
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dopamine Agents
- Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates
- Monoamine Oxidase B Inhibitors
- Monoamine Oxidase Inhibitors
- Nervous System
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acid amides
- Alternative Parents
- Alanine and derivatives / Benzylamines / Phenol ethers / Phenoxy compounds / Phenylmethylamines / Fluorobenzenes / Alkyl aryl ethers / Aralkylamines / Aryl fluorides / Primary carboxylic acid amides show 6 more
- Substituents
- Alanine or derivatives / Alkyl aryl ether / Alpha-amino acid amide / Amine / Aralkylamine / Aromatic homomonocyclic compound / Aryl fluoride / Aryl halide / Benzenoid / Benzylamine show 21 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 90ENL74SIG
- CAS number
- 133865-89-1
- InChI Key
- NEMGRZFTLSKBAP-LBPRGKRZSA-N
- InChI
- 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
- IUPAC Name
- (2S)-2-[({4-[(3-fluorophenyl)methoxy]phenyl}methyl)amino]propanamide
- SMILES
- C[C@H](NCC1=CC=C(OCC2=CC(F)=CC=C2)C=C1)C(N)=O
References
- General References
- Onofrj M, Bonanni L, Thomas A: An expert opinion on safinamide in Parkinson's disease. Expert Opin Investig Drugs. 2008 Jul;17(7):1115-25. doi: 10.1517/13543784.17.7.1115 . [Article]
- Stocchi F, Vacca L, Grassini P, De Pandis MF, Battaglia G, Cattaneo C, Fariello RG: Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition. Neurology. 2006 Oct 10;67(7 Suppl 2):S24-9. [Article]
- Marzo A, Dal Bo L, Monti NC, Crivelli F, Ismaili S, Caccia C, Cattaneo C, Fariello RG: Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity. Pharmacol Res. 2004 Jul;50(1):77-85. [Article]
- Leuratti C, Sardina M, Ventura P, Assandri A, Muller M, Brunner M: Disposition and metabolism of safinamide, a novel drug for Parkinson's disease, in healthy male volunteers. Pharmacology. 2013;92(3-4):207-16. doi: 10.1159/000354805. Epub 2013 Oct 11. [Article]
- Schapira AH: Safinamide in the treatment of Parkinson's disease. Expert Opin Pharmacother. 2010 Sep;11(13):2261-8. doi: 10.1517/14656566.2010.511612. [Article]
- External Links
- PubChem Compound
- 131682
- PubChem Substance
- 347827780
- ChemSpider
- 116349
- BindingDB
- 50078694
- 1922448
- ChEBI
- 134718
- ChEMBL
- CHEMBL396778
- ZINC
- ZINC000053084692
- Wikipedia
- Safinamide
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Idiopathic Parkinson's Disease 1 4 Completed Treatment Parkinson's Disease (PD) 2 4 Recruiting Treatment Idiopathic Parkinson's Disease (at Later Stage) 1 3 Completed Treatment Idiopathic Parkinson's Disease 2 3 Completed Treatment Parkinson's Disease (PD) 4
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet Oral 50 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, coated Oral 100 mg Tablet, film coated Oral 100 MG Tablet, film coated Oral 50 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8278485 No 2012-10-02 2027-06-08 US US8283380 No 2012-10-09 2027-09-01 US US8076515 No 2011-12-13 2028-12-10 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00989 mg/mL ALOGPS logP 2.59 ALOGPS logP 2.48 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 15.76 Chemaxon pKa (Strongest Basic) 7.93 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 64.35 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 83 m3·mol-1 Chemaxon Polarizability 32.16 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0a4i-3960000000-7f5d8f96b3717db044bd Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0pb9-1914000000-1f202ec8db9cb8723335 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0f80-7096000000-8777f624430e7382ca0b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-2690000000-18e70b3c3ee436d0aa6b Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9300000000-f187c48c035ec2d75fb8 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4l-7910000000-9903e8bef2dbc633b0c9 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9600000000-92f9567dd4e2c38b93c9 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 164.71306 predictedDeepCCS 1.0 (2019) [M+H]+ 167.07106 predictedDeepCCS 1.0 (2019) [M+Na]+ 173.63618 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Primary amine oxidase activity
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOB
- Uniprot ID
- P27338
- Uniprot Name
- Amine oxidase [flavin-containing] B
- Molecular Weight
- 58762.475 Da
References
- Marzo A, Dal Bo L, Monti NC, Crivelli F, Ismaili S, Caccia C, Cattaneo C, Fariello RG: Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity. Pharmacol Res. 2004 Jul;50(1):77-85. [Article]
- Authors unspecified: Safinamide: FCE 26743, NW 1015, PNU 151774, PNU 151774E. Drugs R D. 2004;5(6):355-8. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- Leonetti F, Capaldi C, Pisani L, Nicolotti O, Muncipinto G, Stefanachi A, Cellamare S, Caccia C, Carotti A: Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase. J Med Chem. 2007 Oct 4;50(20):4909-16. Epub 2007 Sep 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Leuratti C, Sardina M, Ventura P, Assandri A, Muller M, Brunner M: Disposition and metabolism of safinamide, a novel drug for Parkinson's disease, in healthy male volunteers. Pharmacology. 2013;92(3-4):207-16. doi: 10.1159/000354805. Epub 2013 Oct 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- There is limited data currently available on this enzyme inhibition.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Marzo A, Dal Bo L, Monti NC, Crivelli F, Ismaili S, Caccia C, Cattaneo C, Fariello RG: Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity. Pharmacol Res. 2004 Jul;50(1):77-85. [Article]
- Malek NM, Grosset DG: Investigational agents in the treatment of Parkinson's disease: focus on safinamide. J Exp Pharmacol. 2012 Aug 14;4:85-90. doi: 10.2147/JEP.S34343. eCollection 2012. [Article]
- Safinamide FDA label [File]
- Safinamide, Pharmacology Review, FDA [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- CYP3A5 was inhibited by safinamide metabolites NW-1153 and NW 1689 at >100mcM [FDA Label].
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate (PubMed:10873595). Mediates transport of prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123 an...
- Gene Name
- SLCO3A1
- Uniprot ID
- Q9UIG8
- Uniprot Name
- Solute carrier organic anion transporter family member 3A1
- Molecular Weight
- 76552.135 Da
References
- Leuratti C, Sardina M, Ventura P, Assandri A, Muller M, Brunner M: Disposition and metabolism of safinamide, a novel drug for Parkinson's disease, in healthy male volunteers. Pharmacology. 2013;92(3-4):207-16. doi: 10.1159/000354805. Epub 2013 Oct 11. [Article]
Drug created at March 19, 2008 16:45 / Updated at February 20, 2024 23:55