Selegiline (T3D2965)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2009-07-21 20:28:13 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2965
Identification
Common NameSelegiline
ClassSmall Molecule
DescriptionA selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [PubChem]
Compound Type
  • Amine
  • Antidyskinetic
  • Antiparkinson Agent
  • Central Nervous System Agent
  • Dopaminergic
  • Drug
  • Metabolite
  • Monoamine Oxidase Inhibitor
  • Neuroprotective Agent
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(−)-selegiline
Carbex
Eldepryl
EmSam
Jumex
L-Deprenalin
Selegilina
Selegilinum
Zelapar
Chemical FormulaC13H17N
Average Molecular Mass187.281 g/mol
Monoisotopic Mass187.136 g/mol
CAS Registry Number14611-51-9
IUPAC Namemethyl(1-phenylpropan-2-yl)(prop-2-yn-1-yl)amine
Traditional NameD-deprenyl
SMILESCC(CC1=CC=CC=C1)N(C)CC#C
InChI IdentifierInChI=1/C13H17N/c1-4-10-14(3)12(2)11-13-8-6-5-7-9-13/h1,5-9,12H,10-11H2,2-3H3
InChI KeyInChIKey=MEZLKOACVSPNER-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenethylamines
Direct ParentAmphetamines and derivatives
Alternative Parents
Substituents
  • Amphetamine or derivatives
  • Phenylpropane
  • Aralkylamine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Acetylide
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point141-142°C
Boiling PointNot Available
Solubility2.54e-02 g/L
LogP2.7
Predicted Properties
PropertyValueSource
Water Solubility0.025 g/LALOGPS
logP3.08ALOGPS
logP2.85ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)8.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity61.35 m³·mol⁻¹ChemAxon
Polarizability22.48 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00r5-9200000000-2d93d82c982a8f156fde2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-9000000000-2501a3aa1587896c267f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-9000000000-e47889ea8699fd64eac52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014u-4900000000-394f656868b3e600bd4c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00ko-7900000000-05e9bdebb41aefc9bdd72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-9100000000-802ede31c15020d08f7d2017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-805c85cf8fffbddf9ce32016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kk-6900000000-96dce81a4b7e4f517c3e2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fr6-9300000000-75e40864b8dbd51d70d12016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-24ba7e734753b5935dd42016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-2900000000-c504d7447caf055d67a72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014l-9300000000-8b853bed043b95c3c6bb2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-2900000000-20851b32b820fc9ed4602021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-9000000000-056944dbb701a5e7815a2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-08554ca2f75d51e8c4cd2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-2900000000-b9c2210b820f3a4f784c2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kf-9300000000-952f055a493d5c8adc442021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0gdl-9700000000-c1b8a392ffad5607d6352021-10-11View Spectrum
Toxicity Profile
Route of ExposureOral. Rapidly absorbed from the gastrointestinal tract.
Mechanism of ToxicityAlthough the mechanisms for selegiline's beneficial action in the treatment of Parkinson's disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain. Selegiline binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. Selegiline may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, selegiline can also inhibit monozmine oxidase type A (MAO-A), allowing it to be used for the treatment of depression. MAO's activity is inhibited when selegiline binds to the isoalloxazine flavin adenine dinucleotide (FAD) at its active center
Metabolism Half Life: 1.2-2 hours
Toxicity ValuesLD50: 63 mg/kg (Intravenous, Rat) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMonotherapy for initial treatment of Parkinson's disease, as well as an adjunct therapy in patients with a decreased response to levodopa/carbadopa. Also used for the palliative treatment of mild to moderate Alzheimer's disease and at higher doses, for the treatment of depression.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentTreatment of overdose with non-selective MAOIs is symptomatic and supportive. Induction of emesis or gastric lavage with instillation of charcoal slurry may be helpful in early poisoning, provided the airway has been protected against aspiration. Signs and symptoms of central nervous system stimulation, including convulsions, should be treated with diazepam, given slowly intravenously. Phenothiazine derivatives and central nervous system stimulants should be avoided. Hypotension and vascular collapse should be treated with intravenous fluids and, if necessary, blood pressure titration with an intravenous infusion of a dilute pressor agent. It should be noted that adrenergic agents may produce a markedly increased pressor response. Respiration should be supported by appropriate measures, including management of the airway, use of supplemental oxygen, and mechanical ventilatory assistance, as required. Body temperature should be monitored closely. Intensive management of hyperpyrexia may be required. Maintenance of fluid and electrolyte balance is essential. (9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01037
HMDB IDHMDB15171
PubChem Compound ID5195
ChEMBL IDCHEMBL972
ChemSpider ID5007
KEGG IDC07245
UniProt IDNot Available
OMIM ID
ChEBI ID50217
BioCyc IDNot Available
CTD IDNot Available
Stitch IDSelegiline
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkSelegiline
References
Synthesis Reference

Silvia Ott-Dembrowski, Richard Cyrus, Jorg Schmidt, Hans Waiblinger, “Preparation of selegiline.” U.S. Patent US5847216, issued March, 1962.

MSDSLink
General References
  1. Engberg G, Elebring T, Nissbrandt H: Deprenyl (selegiline), a selective MAO-B inhibitor with active metabolites; effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons. J Pharmacol Exp Ther. 1991 Nov;259(2):841-7. [1658311 ]
  2. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  3. Macleod AD, Counsell CE, Ives N, Stowe R: Monoamine oxidase B inhibitors for early Parkinson's disease. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004898. [16034956 ]
  4. Heinonen EH, Anttila MI, Lammintausta RA: Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):742-9. [7995016 ]
  5. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. Clin Pharmacokinet. 2002;41(4):261-309. [11978145 ]
  6. Culpepper L, Kovalick LJ: A review of the literature on the selegiline transdermal system: an effective and well-tolerated monoamine oxidase inhibitor for the treatment of depression. Prim Care Companion J Clin Psychiatry. 2008;10(1):25-30. [18311418 ]
  7. Lee KC, Chen JJ: Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3(5):527-37. [19300583 ]
  8. Drugs.com [Link]
  9. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Amine oxidase [flavin-containing] B
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 tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
Molecular Weight:
58762.475 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.091 uMNot AvailableBindingDB 15579
Inhibitory0.97 uMNot AvailableBindingDB 15579
Inhibitory1.96 uMNot AvailableBindingDB 15579
IC500.000017 uMNot AvailableBindingDB 15579
IC500.007 uMNot AvailableBindingDB 15579
IC500.013 uMNot AvailableBindingDB 15579
IC500.0148 uMNot AvailableBindingDB 15579
IC500.017 uMNot AvailableBindingDB 15579
IC500.0185 uMNot AvailableBindingDB 15579
IC500.019 uMNot AvailableBindingDB 15579
IC500.0196 uMNot AvailableBindingDB 15579
IC500.01995 uMNot AvailableBindingDB 15579
IC500.02 uMNot AvailableBindingDB 15579
IC500.045 uMNot AvailableBindingDB 15579
IC500.056 uMNot AvailableBindingDB 15579
IC500.079 uMNot AvailableBindingDB 15579
IC500.0852 uMNot AvailableBindingDB 15579
IC500.334 uMNot AvailableBindingDB 15579
IC5019.6 uMNot AvailableBindingDB 15579
References
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Target Details
2. Amine oxidase [flavin-containing] A
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 tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular Weight:
59681.27 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory9.06 uMNot AvailableBindingDB 15579
Inhibitory67.25 uMNot AvailableBindingDB 15579
IC500.06725 uMNot AvailableBindingDB 15579
IC501.2 uMNot AvailableBindingDB 15579
IC5067.25 uMNot AvailableBindingDB 15579
IC5067.6083 uMNot AvailableBindingDB 15579
IC5068.73 uMNot AvailableBindingDB 15579
IC5070.2 uMNot AvailableBindingDB 15579
References
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  8. Santana L, Gonzalez-Diaz H, Quezada E, Uriarte E, Yanez M, Vina D, Orallo F: Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors. J Med Chem. 2008 Nov 13;51(21):6740-51. doi: 10.1021/jm800656v. Epub 2008 Oct 4. [18834112 ]
  9. Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F, Yanez M, Orallo F, Ortuso F, Alcaro S: Chalcones: a valid scaffold for monoamine oxidases inhibitors. J Med Chem. 2009 May 14;52(9):2818-24. doi: 10.1021/jm801590u. [19378991 ]
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  14. Chimenti F, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S, Maccioni E, Cardia MC, Yanez M, Orallo F, Alcaro S, Ortuso F, Cirilli R, Ferretti R, Distinto S, Kirchmair J, Langer T: Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors. Bioorg Med Chem. 2010 Jul 15;18(14):5063-70. doi: 10.1016/j.bmc.2010.05.070. Epub 2010 Jun 1. [20579890 ]
  15. Chimenti F, Bolasco A, Secci D, Chimenti P, Granese A, Carradori S, Yanez M, Orallo F, Ortuso F, Alcaro S: Investigations on the 2-thiazolylhydrazyne scaffold: synthesis and molecular modeling of selective human monoamine oxidase inhibitors. Bioorg Med Chem. 2010 Aug 1;18(15):5715-23. doi: 10.1016/j.bmc.2010.06.007. Epub 2010 Jun 9. [20615716 ]
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  17. Maccioni E, Alcaro S, Orallo F, Cardia MC, Distinto S, Costa G, Yanez M, Sanna ML, Vigo S, Meleddu R, Secci D: Synthesis of new 3-aryl-4,5-dihydropyrazole-1-carbothioamide derivatives. An investigation on their ability to inhibit monoamine oxidase. Eur J Med Chem. 2010 Oct;45(10):4490-8. doi: 10.1016/j.ejmech.2010.07.009. Epub 2010 Jul 17. [20702005 ]
  18. Chimenti F, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S, Yanez M, Orallo F, Sanna ML, Gallinella B, Cirilli R: Synthesis, stereochemical separation, and biological evaluation of selective inhibitors of human MAO-B: 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazines. J Med Chem. 2010 Sep 9;53(17):6516-20. doi: 10.1021/jm100120s. [20715818 ]
  19. Delogu G, Picciau C, Ferino G, Quezada E, Podda G, Uriarte E, Vina D: Synthesis, human monoamine oxidase inhibitory activity and molecular docking studies of 3-heteroarylcoumarin derivatives. Eur J Med Chem. 2011 Apr;46(4):1147-52. doi: 10.1016/j.ejmech.2011.01.033. Epub 2011 Jan 28. [21316817 ]
  20. Desideri N, Bolasco A, Fioravanti R, Monaco LP, Orallo F, Yanez M, Ortuso F, Alcaro S: Homoisoflavonoids: natural scaffolds with potent and selective monoamine oxidase-B inhibition properties. J Med Chem. 2011 Apr 14;54(7):2155-64. doi: 10.1021/jm1013709. Epub 2011 Mar 15. [21405131 ]
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  27. Alcaro S, Gaspar A, Ortuso F, Milhazes N, Orallo F, Uriarte E, Yanez M, Borges F: Chromone-2- and -3-carboxylic acids inhibit differently monoamine oxidases A and B. Bioorg Med Chem Lett. 2010 May 1;20(9):2709-12. doi: 10.1016/j.bmcl.2010.03.081. Epub 2010 Mar 27. [20382016 ]
  28. Gaspar A, Silva T, Yanez M, Vina D, Orallo F, Ortuso F, Uriarte E, Alcaro S, Borges F: Chromone, a privileged scaffold for the development of monoamine oxidase inhibitors. J Med Chem. 2011 Jul 28;54(14):5165-73. doi: 10.1021/jm2004267. Epub 2011 Jul 1. [21696156 ]
  29. Serra S, Ferino G, Matos MJ, Vazquez-Rodriguez S, Delogu G, Vina D, Cadoni E, Santana L, Uriarte E: Hydroxycoumarins as selective MAO-B inhibitors. Bioorg Med Chem Lett. 2012 Jan 1;22(1):258-61. doi: 10.1016/j.bmcl.2011.11.020. Epub 2011 Nov 11. [22137786 ]
  30. Huang L, Lu C, Sun Y, Mao F, Luo Z, Su T, Jiang H, Shan W, Li X: Multitarget-directed benzylideneindanone derivatives: anti-beta-amyloid (Abeta) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer's disease. J Med Chem. 2012 Oct 11;55(19):8483-92. doi: 10.1021/jm300978h. Epub 2012 Oct 1. [22978824 ]
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  32. Mishra N, Sasmal D: Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation. Bioorg Med Chem Lett. 2011 Apr 1;21(7):1969-73. doi: 10.1016/j.bmcl.2011.02.030. Epub 2011 Feb 13. [21377879 ]
Target Details
3. 5-hydroxytryptamine receptor 1A
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 15579
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
Target Details
4. D(1A) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 15579
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]