| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:06:41 |
| Primary Accession Number |
DB01037 |
| Secondary Accession Number |
|
| Name |
Selegiline |
| Drug Type |
- Approved
- Investigational
- Small Molecule
|
| Description |
A 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] |
| Synonyms |
- L-Deprenalin
- Selegeline Hcl
- Selegilina [INN-Spanish]
- Selegilinum [INN-Latin]
- selegiline
|
| Brand Names |
- Apo-Selegiline
- Carbex
- Eldepryl
- Emsam
- Gen-Selegiline
- Jumex
- Novo-Selegiline
- Nu-Selegiline
- Sd Deprenyl
- Zelapar
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
N-methyl-N-[(2R)-1-phenylpropan-2-yl]prop-2-yn-1-amine |
| Chemical Formula |
C13H17N |
| Chemical Structure |
 |
| CAS Registry Number |
14611-51-9 |
| InChI Identifier |
InChI=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/t12-/m1/s1 |
| InChI Key |
MEZLKOACVSPNER-GFCCVEGCBI |
| KEGG Drug |
D03731  |
| KEGG Compound |
C07245  |
| PubChem Compound |
26757  |
| PubChem Substance |
9454  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
Not Available |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02238340  |
| RxList Link |
http://www.rxlist.com/cgi/generic/seleg.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Selegiline  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
Torok Z et al., Acta Pharm Hung. 1992 Sep;62(5):201-11 |
| Average Molecular Weight |
187.2808 |
| Monoisotopic Molecular Weight |
187.1361 |
| State |
Solid |
| Melting Point |
141-142 oC |
| Experimental Water Solubility |
Not Available
Source: PhysProp
|
| Predicted Water Solubility |
2.54e-02 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
2.7
Source: PhysProp
|
| Predicted LogP |
3.08
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-3.87
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
2BK3  |
| Experimental PDB File |
Show |
| Experimental PDB Structure |
|
| Isomeric SMILES |
C[C@H](CC1=CC=CC=C1)N(C)CC#C |
| Canonical SMILES |
CC(CC1=CC=CC=C1)N(C)CC#C |
| Drug Category |
- Antidyskinetics
- Antiparkinson Agents
- Central Nervous System Agents
- Dopaminergics
- Monoamine Oxidase Inhibitors
- Neuroprotective Agents
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For the adjunct treatment for Parkinson's disease and depression. |
| Pharmacology |
Dopamine is an essential chemical that occurs in many parts of the body. It is the premature degradation of dopamine that results in the symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme which accelerates the breakdown of dopamine. Selegiline can prolong the effects of dopamine in the brain by preventing its breakdown through seletively blocking MAO. It also may prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells. |
| Mechanism of Action |
Although the mechanisms for selegiline's beneficial action in the treatment of Parkinson's disease are not fully understood, the 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 is best known as an irreversible inhibitor of MAO. MAO's activity is inhibited when selegiline binds to the isoalloxazine flavin adenine dinucleotide (FAD) at its active center. In addition, there is evidence that selegiline may increase dopaminergic activity through other mechanisms. |
| Absorption |
Rapidly absorbed from the gastrointestinal tract. |
| Toxicity |
LD50=63 mg/kg (rats, IV) |
| Protein Binding |
> 99.5% |
| Biotransformation |
Not Available |
| Half Life |
2 hours |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
Not Available
|
| Food Interactions |
Not Available
|
| Pathways |
Not Available
|
| General References |
- 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. [PubMed
]
- Drugs.com

- Wikipedia

- RxList

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 2C19 (CYP2C19)
- Monoamine oxidase type A (MAO-A)
- Cytochrome P450 2D6 (CYP2D6)
- Cytochrome P450 2B6 (CYP2B6)
- Monoamine oxidase type B (MAO-B)
|
| Targets |
- Amine oxidase [flavin-containing] B
|
|
Phase 1 Metabolizing Enzyme 1
[top]
|
| Enzyme 1 Name |
Cytochrome P450 2C19 (CYP2C19) |
| Enzyme 1 Gene Name |
CYP2C19 |
| Enzyme 1 SwissProt ID |
P33261  |
| Enzyme 1 SNPs |
SNPJam Report  |
| Enzyme 1 Protein Sequence |
>sp|P33261|CP2CJ_HUMAN Cytochrome P450 2C19 (EC 1.14.13.80)
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI
YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM
ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID
LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK
KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP
PFYQLCFIPV
|
|
Phase 1 Metabolizing Enzyme 2
[top]
|
| Enzyme 2 Name |
Monoamine oxidase type A (MAO-A) |
| Enzyme 2 Gene Name |
MAOA |
| Enzyme 2 SwissProt ID |
P21397  |
| Enzyme 2 SNPs |
SNPJam Report  |
| Enzyme 2 Protein Sequence |
>sp|P21397|AOFA_HUMAN Amine oxidase [flavin-containing]
MENQEKASIAGHMFDVVVIGGGISGLSAAKLLTEYGVSVLVLEARDRVGGRTYTIRNEHV
DYVDVGGAYVGPTQNRILRLSKELGIETYKVNVSERLVQYVKGKTYPFRGAFPPVWNPIA
YLDYNNLWRTIDNMGKEIPTDAPWEAQHADKWDKMTMKELIDKICWTKTARRFAYLFVNI
NVTSEPHEVSALWFLWYVKQCGGTTRIFSVTNGGQERKFVGGSGQVSERIMDLLGDQVKL
NHPVTHVDQSSDNIIIETLNHEHYECKYVINAIPPTLTAKIHFRPELPAERNQLIQRLPM
GAVIKCMMYYKEAFWKKKDYCGCMIIEDEDAPISITLDDTKPDGSLPAIMGFILARKADR
LAKLHKEIRKKKICELYAKVLGSQEALHPVHYEEKNWCEEQYSGGCYTAYFPPGIMTQYG
RVIRQPVGRIFFAGTETATKWSGYMEGAVEAGERAAREVLNGLGKVTEKDIWVQEPESKD
VPAVEITHTFWERNLPSVSGLLKIIGFSTSVTALGFVLYKYKLLPRS
|
|
Phase 1 Metabolizing Enzyme 3
[top]
|
| Enzyme 3 Name |
Cytochrome P450 2D6 (CYP2D6) |
| Enzyme 3 Gene Name |
CYP2D6 |
| Enzyme 3 SwissProt ID |
P10635  |
| Enzyme 3 SNPs |
SNPJam Report  |
| Enzyme 3 Protein Sequence |
>sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1)
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
|
|
Phase 1 Metabolizing Enzyme 4
[top]
|
| Enzyme 4 Name |
Cytochrome P450 2B6 (CYP2B6) |
| Enzyme 4 Gene Name |
CYP2B6 |
| Enzyme 4 SwissProt ID |
P20813  |
| Enzyme 4 SNPs |
SNPJam Report  |
| Enzyme 4 Protein Sequence |
>sp|P20813|CP2B6_HUMAN Cytochrome P450 2B6 (EC 1.14.14.1)
MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLRFRE
KYGDVFTVHLGPRPVVMLCGVEAIREALVDKAEAFSGRGKIAMVDPFFRGYGVIFANGNR
WKVLRRFSVTTMRDFGMGKRSVEERIQEEAQCLIEELRKSKGALMDPTFLFQSITANIIC
SIVFGKRFHYQDQEFLKMLNLFYQTFSLISSVFGQLFELFSGFLKYFPGAHRQVYKNLQE
INAYIGHSVEKHRETLDPSAPKDLIDTYLLHMEKEKSNAHSEFSHQNLNLNTLSLFFAGT
ETTSTTLRYGFLLMLKYPHVAERVYREIEQVIGPHRPPELHDRAKMPYTEAVIYEIQRFS
DLLPMGVPHIVTQHTSFRGYIIPKDTEVFLILSTALHDPHYFEKPDAFNPDHFLDANGAL
KKTEAFIPFSLGKRICLGEGIARAELFLFFTTILQNFSMASPVAPEDIDLTPQECGVGKI
PPTYQIRFLPR
|
|
Phase 1 Metabolizing Enzyme 5
[top]
|
| Enzyme 5 Name |
Monoamine oxidase type B (MAO-B) |
| Enzyme 5 Gene Name |
MAOB |
| Enzyme 5 SwissProt ID |
P27338  |
| Enzyme 5 SNPs |
SNPJam Report  |
| Enzyme 5 Protein Sequence |
>sp|P27338|AOFB_HUMAN Amine oxidase B
SNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSYV
GPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWRT
MDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEVS
ALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQT
RENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVYY
KEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEERL
KKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDRI
YFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTTF
LERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
|
|
Drug Target 1
[top]
|
| Target 1 ID |
3939 |
| Target 1 Name |
Amine oxidase [flavin-containing] B |
| Target 1 Synonyms |
- EC 1.4.3.4
- MAO-B
- Monoamine oxidase type B
|
| Target 1 Gene Name |
MAOB |
| Target 1 Protein Sequence |
>Amine oxidase [flavin-containing] B
MSNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSY
VGPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWR
TMDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEV
SALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQ
TRENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVY
YKEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEER
LKKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDR
IYFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTT
FLERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
|
| Target 1 Number of Residues |
528 |
| Target 1 Molecular Weight |
58764 |
| Target 1 Theoretical pI |
7.55 |
| Target 1 GO Classification |
|
Function
|
catalytic activity
oxidoreductase activity |
|
Process
|
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport |
|
Component
|
| Not Available |
|
| Target 1 General Function |
Amino acid transport and metabolism |
| Target 1 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 |
| Target 1 Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Tryptophan metabolism |
|
map00220  |
|
| Target 1 Reactions |
- RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2
|
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
398415  |
| Target 1 UniProtKB/Swiss-Prot ID |
P27338  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
AOFB_HUMAN  |
| Target 1 PDB ID |
2BK3  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
|
| Target 1 Gene Sequence |
>1560 bp
ATGAGCAACAAATGCGACGTGGTCGTGGTGGGGGGCGGCATCTCAGGTATGGCAGCAGCC
AAACTTCTGCATGACTCTGGACTGAATGTGGTTGTTCTGGAAGCCCGGGACCGTGTGGGA
GGCAGGACTTACACTCTTAGGAACCAAAAGGTTAAATATGTGGACCTTGGAGGATCCTAT
GTTGGACCAACCCAGAATCGTATCTTGAGATTAGCCAAGGAGCTAGGATTGGAGACCTAC
AAAGTGAATGAGGTTGAGCGTCTGATCCACCATGTAAAGGGCAAATCATACCCCTTCAGG
GGGCCATTCCCACCTGTATGGAATCCAATTACCTACTTAGATCATAACAACTTTTGGAGG
ACAATGGATGACATGGGGCGAGAGATTCCGAGTGATGCCCCATGGAAGGCTCCCCTTGCA
GAAGAGTGGGACAACATGACAATGAAGGAGCTACTGGACAAGCTCTGCTGGACTGAATCT
GCAAAGCAGCTTGCCACTCTCTTTGTGAACCTGTGTGTCACTGCAGAGACCCATGAGGTC
TCTGCTCTCTGGTTCCTGTGGTATGTGAAGCAGTGTGGAGGCACAACAAGAATCATCTCG
ACAACAAATGGAGGACAGGAGAGGAAATTTGTGGGCGGATCTGGTCAAGTGAGTGAGCGG
ATAATGGACCTCCTTGGAGACCGAGTGAAGCTGGAGAGGCCTGTGATCTACATTGACCAG
ACAAGAGAAAATGTCCTTGTGGAGACCCTAAACCATGAGATGTATGAGGCTAAATATGTG
ATTAGTGCTATTCCTCCTACTCTGGGCATGAAGATTCACTTCAATCCCCCTCTGCCAATG
ATGAGAAACCAGATGATCACTCGTGTGCCTTTGGGTTCAGTCATCAAGTGTATAGTTTAT
TATAAAGAGCCTTTCTGGAGGAAAAAGGATTACTGTGGAACCATGATTATTGATGGAGAA
GAAGCTCCAGTTGCCTACACGTTGGATGATACCAAACCTGAAGGCAACTATGCTGCCATA
ATGGGATTTATCCTGGCCCACAAAGCCAGAAAACTGGCACGTCTTACCAAAGAGGAAAGG
TTGAAGAAACTTTGTGAACTCTATGCCAAGGTTCTGGGTTCCCTAGAAGCTCTGGAGCCA
GTGCATTATGAAGAAAAGAACTGGTGTGAGGAGCAGTACTCTGGGGGCTGCTACACAACT
TATTTCCCCCCTGGGATCCTGACTCAATATGGAAGGGTTCTACGCCAGCCAGTGGACAGG
ATTTACTTTGCAGGCACCGAGACTGCCACACACTGGAGCGGCTACATGGAGGGGGCTGTA
GAGGCCGGGGAGAGAGCAGCCCGAGAGATCCTGCATGCCATGGGGAAGATTCCAGAGGAT
GAAATCTGGCAGTCAGAACCAGAGTCTGTGGATGTCCCTGCACAGCCCATCACCACCACC
TTTTTGGAGAGACATTTGCCCTCCGTGCCAGGCCTGCTCAGGCTGATTGGATTGACCACC
ATCTTTTCAGCAACGGCTCTTGGCTTCCTGGCCCACAAAAGGGGGCTACTTGTGAGAGTC
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
MAOB  |
| Target 1 GenAtlas ID |
MAOB  |
| Target 1 HGNC ID |
HGNC:6834  |
| Target 1 Chromosome Location |
X |
| Target 1 Locus |
Xp11.23 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Newton-Vinson P, Hubalek F, Edmondson DE: High-level expression of human liver monoamine oxidase B in Pichia pastoris. Protein Expr Purif. 2000 Nov;20(2):334-45. [PubMed
]
- Binda C, Newton-Vinson P, Hubalek F, Edmondson DE, Mattevi A: Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Nat Struct Biol. 2002 Jan;9(1):22-6. [PubMed
]
- Zhu QS, Grimsby J, Chen K, Shih JC: Promoter organization and activity of human monoamine oxidase (MAO) A and B genes. J Neurosci. 1992 Nov;12(11):4437-46. [PubMed
]
- Grimsby J, Chen K, Wang LJ, Lan NC, Shih JC: Human monoamine oxidase A and B genes exhibit identical exon-intron organization. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3637-41. [PubMed
]
- Bach AW, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC: cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4934-8. [PubMed
]
- Chen K, Wu HF, Shih JC: The deduced amino acid sequences of human platelet and frontal cortex monoamine oxidase B are identical. J Neurochem. 1993 Jul;61(1):187-90. [PubMed
]
|
| Target 1 Drug References |
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed
]
|