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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
- Not Available
Interactions
- Drug Interactions
- 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 50 mg Oral Valeo Pharma Corp. 2019-07-08 Not applicable Canada 
Onstryv Tablet 100 mg Oral Valeo Pharma Corp. 2019-07-08 Not applicable Canada Xadago Tablet, film coated 100 mg Oral Zambon S.P.A. 2020-12-18 Not applicable EU 
Xadago Tablet, film coated 100 mg/1 Oral Catalent Germany Schorndorf GmbH 2017-05-08 2018-02-05 US 
Xadago Tablet, film coated 100 mg Oral Zambon S.P.A. 2021-01-27 Not applicable EU
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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Recruiting Not Available Parkinson's Disease (PD) 1 somestatus stop reason just information to hide 4 Completed Treatment Idiopathic Parkinson's Disease 1 somestatus stop reason just information to hide 4 Completed Treatment Parkinson's Disease (PD) 2 somestatus stop reason just information to hide 4 Recruiting Treatment Idiopathic Parkinson's Disease (at Later Stage) 1 somestatus stop reason just information to hide 3 Completed Treatment Idiopathic Parkinson's Disease 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 65.88 MG 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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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924). Preferentially degrades benzylamine and phenylethylamine (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924)
- Specific Function
- Aliphatic amine oxidase activity
- 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
- Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:18391214, PubMed:20493079, PubMed:24169519, PubMed:8316221). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity)
- Specific Function
- Aliphatic amine oxidase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
- Specific Function
- Arachidonic acid monooxygenase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- Aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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 imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 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
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- Aromatase activity
- 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
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Putative organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormone L-thyroxine, prostanoids such as prostaglandin E1 and E2, bile acids such as taurocholate, glycolate and glycochenodeoxycholate and peptide hormones such as L-arginine vasopressin, likely operating in a tissue-specific manner (PubMed:10873595, PubMed:14631946, PubMed:16971491, PubMed:19129463, PubMed:30063921). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable)
- Specific Function
- Organic anion transmembrane transporter activity
- 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 April 23, 2024 11:38