Tmic
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Record Information
Version2.0
Creation Date2009-07-30 17:58:35 UTC
Update Date2014-12-24 20:26:06 UTC
Accession NumberT3D3474
Identification
Common Name1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
ClassSmall Molecule
Description1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes permanent symptoms of Parkinson's disease by killing certain neurons in the substantia nigra of the brain. While MPTP itself does not have opioid effects, it is related to MPPP, a synthetic opioid drug with effects similar to those of heroin and morphine. MPTP can be accidentally produced during the illicit manufacture of MPPP, and that is how its Parkinson-inducing effects were first discovered. MPTP is used to recreate and study the Parkinson's disease in experimental animal models. (2)
Compound Type
  • Amine
  • Industrial Precursor/Intermediate
  • Industrial/Workplace Toxin
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,2,3,6-Tetrahydro-1-methyl-4-phenylpyridine
MPTP
N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Chemical FormulaC12H15N
Average Molecular Mass173.254 g/mol
Monoisotopic Mass173.120 g/mol
CAS Registry Number28289-54-5
IUPAC Name1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Traditional NameMPTP
SMILESCN1CCC(=CC1)C1=CC=CC=C1
InChI IdentifierInChI=1S/C12H15N/c1-13-9-7-12(8-10-13)11-5-3-2-4-6-11/h2-7H,8-10H2,1H3
InChI KeyInChIKey=PLRACCBDVIHHLZ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as hydropyridines. Hydropyridines are compounds containing a hydrogenated pyridine ring (i.e. containing less than the maximum number of double bonds.).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassHydropyridines
Direct ParentHydropyridines
Alternative Parents
Substituents
  • Benzenoid
  • Hydropyridine
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point40-42°C
Boiling Point85-90 °C (at 0.8 mm Hg)
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility6.42 g/LALOGPS
logP2.69ALOGPS
logP2.35ChemAxon
logS-1.4ALOGPS
pKa (Strongest Basic)8.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity57.47 m³·mol⁻¹ChemAxon
Polarizability21.02 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0900000000-e201fc2a2d42013379aaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-2900000000-99d91f9b67fcd6f34a76View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0gb9-8900000000-099735f9e4fb38becc8fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0900000000-d4230bc243608beca34fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0900000000-f32b038842a79e5b2695View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05dl-5900000000-3b4830d260c28b17374cView in MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityMPTP itself is not toxic, and as a lipophilic compound can cross the blood-brain barrier. Once inside the brain, MPTP is metabolized into the toxic cation 1-methyl-4-phenylpyridinium (MPP+) by the enzyme MAO-B of glial cells. MPP+ primarily kills dopamine-producing neurons in a part of the brain called the pars compacta of the substantia nigra. MPP+ interferes with complex I of the electron transport chain, a component of mitochondrial metabolism, which leads to cell death and causes the buildup of free radicals, toxic molecules that contribute further to cell destruction. (2)
MetabolismIn the brain, MPTP is metabolized into the toxic cation 1-methyl-4-phenylpyridinium (MPP+) by the enzyme MAO-B of glial cells. (2)
Toxicity ValuesLD50: 54 mg/kg (Subcutaneous, Mouse) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/Sources1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes permanent symptoms of Parkinson's disease by killing certain neurons in the substantia nigra of the brain. MPTP can be accidentally produced during the illicit manufacture of MPPP, and that is how its Parkinson-inducing effects were first discovered. MPTP is used to recreate and study the Parkinson's disease in experimental animal models.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentBecause MPTP itself is not directly harmful, toxic effects of acute MPTP poisoning can be mitigated by the administration of monoamine oxidase inhibitors (MAOIs) such as selegiline. MAOIs prevent the metabolism of MPTP to MPP+ by inhibiting the action of MAO-B, minimizing toxicity and preventing neural death. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID1388
ChEMBL IDCHEMBL24172
ChemSpider ID1346
KEGG IDC04599
UniProt IDNot Available
OMIM ID
ChEBI ID17963
BioCyc IDNot Available
CTD IDNot Available
Stitch ID1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
PDB IDNot Available
ACToR IDNot Available
Wikipedia Link1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
References
Synthesis ReferenceNot Available
MSDST3D3474.pdf
General References
  1. Fuller RW, Hemrick-Luecke SK: Tissue concentrations of MPTP and MPP+ after administration of lethal and sublethal doses of MPTP to mice. Toxicol Lett. 1990 Dec;54(2-3):253-62. [2124381 ]
  2. Wikipedia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Last Updated 18 July 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

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
Inhibitory280 uMNot AvailableBindingDB 50003599
Inhibitory500 uMNot AvailableBindingDB 50003599
References
  1. Chiba K, Trevor A, Castagnoli N Jr: Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem Biophys Res Commun. 1984 Apr 30;120(2):574-8. [6428396 ]
  2. Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC: Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature. 1984 Oct 4-10;311(5985):467-9. [6332989 ]
  3. Singer TP, Ramsay RR: Mechanism of the neurotoxicity of MPTP. An update. FEBS Lett. 1990 Nov 12;274(1-2):1-8. [2253761 ]
  4. Ogunrombi MO, Malan SF, Terre'Blanche G, Castagnoli K, Castagnoli N Jr, Bergh JJ, Petzer JP: Neurotoxicity studies with the monoamine oxidase B substrate 1-methyl-3-phenyl-3-pyrroline. Life Sci. 2007 Jul 19;81(6):458-67. Epub 2007 Jun 28. [17655878 ]
  5. Hiebert CK, Silverman RB: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues. Inactivation of monoamine oxidase by conformationally rigid analogues of N,N-dimethylcinnamylamine. J Med Chem. 1988 Aug;31(8):1566-70. [3260955 ]