2′-CH3-MPTP

2′-CH₃-MPTP
Clinical data
Other names	2′-Methyl-MPTP
Drug class	Dopaminergic neurotoxin
Identifiers
	IUPAC name 1-methyl-4-(2-methylphenyl)-3,6-dihydro-2H-pyridine;
CAS Number	102417-86-7 ;
PubChem CID	91767;
ChemSpider	82864;
UNII	HGQ85CV4U5;
ChEMBL	ChEMBL60303;
CompTox Dashboard (EPA)	DTXSID70877241 ;
Chemical and physical data
Formula	C13H17N
Molar mass	187.286 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC=CC=C1C2=CCN(CC2)C;
	InChI InChI=1S/C13H17N/c1-11-5-3-4-6-13(11)12-7-9-14(2)10-8-12/h3-7H,8-10H2,1-2H3; Key:BORHNVHYIYTKKC-UHFFFAOYSA-N;

2′-CH₃-MPTP, also known as 2′-methyl-MPTP, is a selective dopaminergic neurotoxin related to MPTP which is used in scientific research to lesion dopaminergic neurons.^[1]^[2] It is a considerably more potent dopaminergic neurotoxin than MPTP in mice but is less potent than MPTP in primates.^[3]^[1]^[4]^[5] MPTP and 2′-CH₃-MPTP produce a Parkinson's disease-like condition in animals.^[6]^[7]

2′-CH₃-MPTP is metabolized by monoamine oxidase A (MAO-A) and B (MAO-B) and this biotransformation is required for its dopaminergic neurotoxicity.^[1]^[8] Whereas the dopaminergic neurotoxicity of MPTP is completely prevented by the MAO-B inhibitor selegiline, complete prevention of 2′-CH₃-MPTP's dopaminergic neurotoxicity requires combined treatment with both selegiline and the MAO-A inhibitor clorgyline.^[8]^[9]

A close analogue of 2′-CH₃-MPTP is 2′-NH₂-MPTP, which, in contrast to 2′-CH₃-MPTP and MPTP, is a serotonergic and noradrenergic neurotoxin with no effect on dopaminergic neurons.^[10] Numerous other neurotoxic MPTP analogues have also been synthesized.^[8]

2′-CH₃-MPTP was first described in the scientific literature by 1986.^[4]

References

^ ^a ^b ^c Maret G, Testa B, Jenner P, el Tayar N, Carrupt PA (1990). "The MPTP story: MAO activates tetrahydropyridine derivatives to toxins causing parkinsonism". Drug Metabolism Reviews. 22 (4): 291–332. doi:10.3109/03602539009041087. PMID 2253555.
^ Manaye KF, Sonsalla PK, Barnett G, Heikkila RE, Woodward DJ, Smith WK, et al. (July 1989). "1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP)-induced degeneration of mesostriatal dopaminergic neurons in the mouse: biochemical and neuroanatomical studies". Brain Research. 491 (2): 307–315. doi:10.1016/0006-8993(89)90065-6. PMID 2765888.
^ Heikkila RE, Sieber BA, Manzino L, Sonsalla PK (June 1989). "Some features of the nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse". Molecular and Chemical Neuropathology. 10 (3): 171–183. doi:10.1007/BF03159727. PMID 2669769.
^ ^a ^b Youngster SK, Duvoisin RC, Hess A, Sonsalla PK, Kindt MV, Heikkila RE (March 1986). "1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) is a more potent dopaminergic neurotoxin than MPTP in mice". European Journal of Pharmacology. 122 (2): 283–287. doi:10.1016/0014-2999(86)90115-9. PMID 3486770.
^ Rose S, Nomoto M, Jackson EA, Gibb WR, Jenner P, Marsden CD (May 1990). "1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) is less neurotoxic than MPTP in the common marmoset". European Journal of Pharmacology. 181 (1–2): 97–103. doi:10.1016/0014-2999(90)90249-6. PMID 2117541.
^ Meredith GE, Rademacher DJ (2011). "MPTP mouse models of Parkinson's disease: an update". Journal of Parkinson's Disease. 1 (1): 19–33. doi:10.3233/JPD-2011-11023. PMC 3530193. PMID 23275799.
^ Herlinger AL, Almeida AR, Presti-Silva SM, Pereira EV, Andrich F, Pires RG, et al. (March 2018). "Behavioral, Biochemical and Molecular Characterization of a Parkinson's Disease Mouse Model Using the Neurotoxin 2'-CH₃-MPTP: A Novel Approach". Neuromolecular Medicine. 20 (1): 73–82. doi:10.1007/s12017-018-8476-z. PMID 29332269.
^ ^a ^b ^c Singer TP, Ramsay RR (November 1990). "Mechanism of the neurotoxicity of MPTP. An update". FEBS Letters. 274 (1–2): 1–8. doi:10.1016/0014-5793(90)81315-f. PMID 2253761.
^ Chiueh CC, Huang SJ, Murphy DL (August 1992). "Enhanced hydroxyl radical generation by 2'-methyl analog of MPTP: suppression by clorgyline and deprenyl". Synapse. 11 (4): 346–348. doi:10.1002/syn.890110410. PMID 1323883.
^ Andrews AM, Murphy DL (March 1993). "Sustained depletion of cortical and hippocampal serotonin and norepinephrine but not striatal dopamine by 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP): a comparative study with 2'-CH3-MPTP and MPTP". Journal of Neurochemistry. 60 (3): 1167–1170. doi:10.1111/j.1471-4159.1993.tb03271.x. PMID 8094744.

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[MaretTestaJenner1990-1] Maret G, Testa B, Jenner P, el Tayar N, Carrupt PA (1990). "The MPTP story: MAO activates tetrahydropyridine derivatives to toxins causing parkinsonism". Drug Metabolism Reviews. 22 (4): 291–332. doi:10.3109/03602539009041087. PMID 2253555.

[ManayeSonsallaBarnett1989-2] Manaye KF, Sonsalla PK, Barnett G, Heikkila RE, Woodward DJ, Smith WK, et al. (July 1989). "1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP)-induced degeneration of mesostriatal dopaminergic neurons in the mouse: biochemical and neuroanatomical studies". Brain Research. 491 (2): 307–315. doi:10.1016/0006-8993(89)90065-6. PMID 2765888.

[HeikkilaSieberManzino1989-3] Heikkila RE, Sieber BA, Manzino L, Sonsalla PK (June 1989). "Some features of the nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse". Molecular and Chemical Neuropathology. 10 (3): 171–183. doi:10.1007/BF03159727. PMID 2669769.

[YoungsterDuvoisinHess1986-4] Youngster SK, Duvoisin RC, Hess A, Sonsalla PK, Kindt MV, Heikkila RE (March 1986). "1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) is a more potent dopaminergic neurotoxin than MPTP in mice". European Journal of Pharmacology. 122 (2): 283–287. doi:10.1016/0014-2999(86)90115-9. PMID 3486770.

[RoseNomotoJackson1990-5] Rose S, Nomoto M, Jackson EA, Gibb WR, Jenner P, Marsden CD (May 1990). "1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) is less neurotoxic than MPTP in the common marmoset". European Journal of Pharmacology. 181 (1–2): 97–103. doi:10.1016/0014-2999(90)90249-6. PMID 2117541.

[MeredithRademacher2011-6] Meredith GE, Rademacher DJ (2011). "MPTP mouse models of Parkinson's disease: an update". Journal of Parkinson's Disease. 1 (1): 19–33. doi:10.3233/JPD-2011-11023. PMC 3530193. PMID 23275799.

[HerlingerAlmeidaPresti-Silva2018-7] Herlinger AL, Almeida AR, Presti-Silva SM, Pereira EV, Andrich F, Pires RG, et al. (March 2018). "Behavioral, Biochemical and Molecular Characterization of a Parkinson's Disease Mouse Model Using the Neurotoxin 2'-CH₃-MPTP: A Novel Approach". Neuromolecular Medicine. 20 (1): 73–82. doi:10.1007/s12017-018-8476-z. PMID 29332269.

[SingerRamsay1990-8] Singer TP, Ramsay RR (November 1990). "Mechanism of the neurotoxicity of MPTP. An update". FEBS Letters. 274 (1–2): 1–8. doi:10.1016/0014-5793(90)81315-f. PMID 2253761.

[ChiuehHUangMurphy1992-9] Chiueh CC, Huang SJ, Murphy DL (August 1992). "Enhanced hydroxyl radical generation by 2'-methyl analog of MPTP: suppression by clorgyline and deprenyl". Synapse. 11 (4): 346–348. doi:10.1002/syn.890110410. PMID 1323883.

[AndrewsMurphy1993-10] Andrews AM, Murphy DL (March 1993). "Sustained depletion of cortical and hippocampal serotonin and norepinephrine but not striatal dopamine by 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP): a comparative study with 2'-CH3-MPTP and MPTP". Journal of Neurochemistry. 60 (3): 1167–1170. doi:10.1111/j.1471-4159.1993.tb03271.x. PMID 8094744.

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2′-CH3-MPTP

References

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