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1,2,3,6-Tetrahydro-1-methyl-4-phenylpyridin

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

HCID 1388
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Grundinformationen

CAS
28289-54-5
Standard-SMILES
CN1CC=C(c2ccccc2)CC1
InChIKey
PLRACCBDVIHHLZ-UHFFFAOYSA-N
Summenformel
C12H15N
Durchschnittliche Molmasse
173,25 g/mol
Monoisotopische Masse
173,12044948

Überblick

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is a tetrahydropyridine that is 1,2,3,6-tetrahydropyridine substituted by a methyl group at position 1 and a phenyl group at position 4. It has a role as a neurotoxin. It is a member of methylpyridines, a tetrahydropyridine and a phenylpyridine.

Namen und Bezeichner

Bevorzugter Name
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
IUPAC
1-methyl-4-phenyl-3,6-dihydro-2H-pyridine
Lokaler Name
1,2,3,6-Tetrahydro-1-methyl-4-phenylpyridin
Englischer Name
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Summenformel
C12H15N
Molmasse
173.25

Namen und Synonyme

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine28289-54-5MPTPPYRIDINE, 1,2,3,6-TETRAHYDRO-1-METHYL-4-PHENYL-1,2,3,6-Tetrahydro-1-methyl-4-phenylpyridineDTXSID8040933N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine9P21XSP91PNSC-139654CHEBI:17963RefChem:76325DTXCID6020933
Weitere Namen anzeigen
NSC 139654Naphthoic Acid Impurity 1111-Methyl-4-phenyl-1,2,3,6-tetrahydropyridin1,2,3,6-tetrahydro-1-methyl-4-phenyl-pyridin1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDRO-PYRIDINEN-METHYL-4-PHENYL-1,2,3,6-TETRAHYDRO-PYRIDINE
248-939-71-methyl-4-phenyl-3,6-dihydro-2H-pyridine1-METHYL-4-PHENYL-PIPERIDINE-3-ENCCRIS 2186HSDB 6942CHEMBL241721-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine1-Methyl-4-phenyl-1,2,3,6-tetrahydroxpyridine

Datenbank-Bezeichner

CAS
28289-54-5

Eigenschaften

Berechnete Struktureigenschaften

XLogP
2,7
Polarare Oberfläche (TPSA)
3,2 Ų
H-Brücken-Donoren
0
H-Brücken-Akzeptoren
1
Frei drehbare Bindungen
1
Schwere Atome
13
Formalladung
0
Komplexität
189

Experimentelle und physikochemische Eigenschaften

Chemical ClassesNitrogen Compounds -> Pyridines
DrugsDEA NFLIS-Drug Category -> Narcotics
LogPlog Kow = 2.71 @ pH 7.5 (as MPP+)
Color/FormCrystals from heptane
Boiling Point85 to 90 °C @ 0.8 mm Hg
Melting Point40-42 °C
Vapor Pressure0.00945 [mmHg]
Physical DescriptionCrystals; [HSDB]

Physikochemische Eigenschaften

Schmelzpunkt
36 °C · aprox. 36°C
Siedepunkt
128 · 128-132 °C12 mm Hg(lit.)
Dichte
1.001 · 1.001±0.06 g/cm3(Predicted)

Sicherheit und Regulatorisches

Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.

GHS-Klassifizierung

GHS Classification · 4 Einträge

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P260, P264, P270, P301+P316, P308+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Gefahrenhinweise

Hazards Summary · 1 Eintrag

The toxic effects of MPTP were discovered in 1982 when several injection drug users in San Jose, California developed frozen addict syndrome within a week of using MPPP contaminated with MPTP. The syndrome resembled idiopathic Parkinson disease, and patients showed some improvement after treatment with L-dopa. [Ford, p. 634-5] MPTP does not cause occupational parkinsonism, but it causes acute parkinsonism in humans and experimental animals after injection. The cumulative doses in animals are in the range of 1.5 to 410 mg/kg depending on the species. [See Reference #1}

Hazard Classes and CategoriesAcute Tox. 3 (100%)

Sicherheit und Schutzausrüstung

Disposal Methods · 1 Eintrag

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Toxikologische Informationen

Chemie und Industrie

Pharmakologische Informationen

Metabolism/Metabolites · 2 Einträge

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine has known human metabolites that include p-hydroxy-MPTP and 1-methyl-4-phenylpyridin-1-ium.

In the brain, MPTP is metabolized into the toxic cation 1-methyl-4-phenylpyridinium (MPP+) by the enzyme MAO-B of glial cells. (L1670)

MeSH Pharmacological Classification · 2 Einträge

Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.

Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.

Verwendung und Herstellung

Uses · 2 Einträge

A contaminant produced during the synthesis of MPPP, a synthetic heroin; it causes irreversible parkinsonism in primates and is used in research laboratories; MPTP is converted to the toxic metabolite MPP+ in the brain where it selectively destroys cells in the substantia nigra. [Merck Index #6294]

1-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.

Methods of ManufacturingPrepn as hydrochloride by Grignard reaction: A Ziering et al, J Org Chem 12, 894 (1947). Alternative prepn: CJ Schmidle, RC Mansfield, J Am Chem Soc 78, 425 (1956).
General Manufacturing InformationIdentification as impurity in "synthetic heroin".

Anwendungen

Zugehörige Reaktionen

9
Reaktionsaufzeichnung erstellen
Reaktionsgleichung von HRID 225222
HRID 225222als Eduktuspto-grants-1980_11
Reaktionsgleichung von HRID 669905
HRID 669905als ProduktTraining data from https://doi.org/10.1039/C8SC04228D (3/10)
Reaktionsgleichung von HRID 1277525
HRID 1277525als Eduktuspto-grants-1981_07
Reaktionsgleichung von HRID 1568962
HRID 1568962als EduktTraining data from https://doi.org/10.1039/C8SC04228D (1/10)
Reaktionsgleichung von HRID 1980093
HRID 1980093als Eduktuspto-grants-1984_11
Reaktionsgleichung von HRID 2134151
HRID 2134151als EduktTraining data from https://doi.org/10.1039/C8SC04228D (4/10)
Reaktionsgleichung von HRID 2150391
HRID 2150391als EduktTraining data from https://doi.org/10.1039/C8SC04228D (4/10)
Reaktionsgleichung von HRID 2163137
HRID 2163137als Produktuspto-grants-1979_01
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Auf dieser SeiteGrundinformationenÜberblickNamen und BezeichnerEigenschaftenSicherheit und RegulatorischesChemie und IndustrieZugehörige ReaktionenNotizen zur Verbindung
PubChem CID
1388
DTXSID
DTXSID8040933
ChEMBL
CHEMBL24172
ChEBI
CHEBI:17963
UNII
9P21XSP91P
EC Number
248-939-7
Nikkaji
J22.909A
storage temp.
Inert atmosphere,Room Temperature
Löslichkeit
Chloroform (Slightly), Dichloromethane (Slightly), Ethyl Acetate (Slightly)
pka
8.66 · 8.66±0.40(Predicted)
Aggregatzustand
Solid
Farbe
Pale Yellow to Light Yellow
Merck
13 · 13,6319
Stabilität
Stable. Incompatible with strong oxidizing agents.
Treatment · 1 Eintrag

Because 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. (L1670)

Adverse EffectsNeurotoxin - Parkinsonism
Toxicity Summary · 1 Eintrag

MPTP 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. (L1670)

Human Toxicity Excerpts · 1 Eintrag

chemical selective damage to cells in the substantia nigra occurs following human ingestion of MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine). ... Following iv injection of an illicit drug containing MPTP, humans developed chronic Parkinsonism, resulting from substantia nigra destruction.

Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Antidote and Emergency Treatment · 2 Einträge

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

Toxicity DataLD50: 54 mg/kg (Subcutaneous, Mouse) (A2830)

Sicherheitsdaten

wgk
3
ridadr
UN 2811 6.1/PG 2
RTECS-Nr.
UT8358900
risk_code
25-39/23/24/25
Toxizität
Human toxicity originally discovered when it was an unexpected by-product from the illicit synthesis of a heroin substitute (i.e., meperidine analog). Currently used experimentally as the primary animal model for the study of Parkinson’s disease. MPTP is a neurotoxicant that is activated to 1-methyl-4-phenylpyridinium ion (MPP1) by the actions of monoamine oxidase B located in the mitochondria of brain astrocytes. The MPP1 is then transported into dopamine, and to a lesser extent, other monoaminergic neurons. Once inside these dopamine neurons in the substantia nigra, it destroys these neurons by mechanisms that may involve an oxidative cascade and/or inhibition of electron transport. Intoxication causes a parkinsonism syndrome almost identical in signs and symptoms to Parkinson’s disease, including rigidity, bradykinesia, tremor, and postural instability. In the event of known ingestion, immediate (but not delayed) administration of a monoamine oxidase inhibitor (especially one selective for MAO-B like deprenyl) and dopamine uptake inhibitor can be therapeutic.
hazard_code
T
safety_code
45
hazard_class
6.1(b)
packing_group
III
Giftige Stoffe Daten
28289-54-5(Hazardous Substances Data)

Verwenden1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine is a dopaminergic neurotoxin that reportedly causes a severe and irreversible Parkinsonian condition in humans and monkeys.

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Ergänzende Hinweise

DefinitionChEBI: A tetrahydropyridine that is 1,2,3,6-tetrahydropyridine substituted by a methyl group at position 1 and a phenyl group at position 4.