2′-CH3-MPTP

{{Short description|Dopaminergic neurotoxin}}

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{{DISPLAYTITLE:2′-CH₃-MPTP}}

{{Infobox drug

| drug_name = 2′-CH₃-MPTP

| image = 2′-CH3-MPTP.svg

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| class = Dopaminergic neurotoxin

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 102417-86-7

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| UNII = HGQ85CV4U5

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| PubChem = 91767

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| ChemSpiderID = 82864

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| ChEMBL = 60303

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| synonyms = 2′-Methyl-MPTP

| IUPAC_name = 1-methyl-4-(2-methylphenyl)-3,6-dihydro-2H-pyridine

| C=13 | H=17 | N=1

| SMILES = CC1=CC=CC=C1C2=CCN(CC2)C

| StdInChI = 1S/C13H17N/c1-11-5-3-4-6-13(11)12-7-9-14(2)10-8-12/h3-7H,8-10H2,1-2H3

| StdInChIKey = 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.{{cite journal | vauthors = Maret G, Testa B, Jenner P, el Tayar N, Carrupt PA | title = The MPTP story: MAO activates tetrahydropyridine derivatives to toxins causing parkinsonism | journal = Drug Metabolism Reviews | volume = 22 | issue = 4 | pages = 291–332 | date = 1990 | pmid = 2253555 | doi = 10.3109/03602539009041087 }}{{cite journal | vauthors = Manaye KF, Sonsalla PK, Barnett G, Heikkila RE, Woodward DJ, Smith WK, German DC | title = 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 | journal = Brain Research | volume = 491 | issue = 2 | pages = 307–315 | date = July 1989 | pmid = 2765888 | doi = 10.1016/0006-8993(89)90065-6 }} It is a considerably more potent dopaminergic neurotoxin than MPTP in mice but is less potent than MPTP in primates.{{cite journal | vauthors = Heikkila RE, Sieber BA, Manzino L, Sonsalla PK | title = Some features of the nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse | journal = Molecular and Chemical Neuropathology | volume = 10 | issue = 3 | pages = 171–183 | date = June 1989 | pmid = 2669769 | doi = 10.1007/BF03159727 }}{{cite journal | vauthors = Youngster SK, Duvoisin RC, Hess A, Sonsalla PK, Kindt MV, Heikkila RE | title = 1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) is a more potent dopaminergic neurotoxin than MPTP in mice | journal = European Journal of Pharmacology | volume = 122 | issue = 2 | pages = 283–287 | date = March 1986 | pmid = 3486770 | doi = 10.1016/0014-2999(86)90115-9 }}{{cite journal | vauthors = Rose S, Nomoto M, Jackson EA, Gibb WR, Jenner P, Marsden CD | title = 1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) is less neurotoxic than MPTP in the common marmoset | journal = European Journal of Pharmacology | volume = 181 | issue = 1–2 | pages = 97–103 | date = May 1990 | pmid = 2117541 | doi = 10.1016/0014-2999(90)90249-6 }} MPTP and 2′-CH₃-MPTP produce a Parkinson's disease-like condition in animals.{{cite journal | vauthors = Meredith GE, Rademacher DJ | title = MPTP mouse models of Parkinson's disease: an update | journal = Journal of Parkinson's Disease | volume = 1 | issue = 1 | pages = 19–33 | date = 2011 | pmid = 23275799 | pmc = 3530193 | doi = 10.3233/JPD-2011-11023 }}{{cite journal | vauthors = Herlinger AL, Almeida AR, Presti-Silva SM, Pereira EV, Andrich F, Pires RG, Martins-Silva C | title = Behavioral, Biochemical and Molecular Characterization of a Parkinson's Disease Mouse Model Using the Neurotoxin 2'-CH₃-MPTP: A Novel Approach | journal = Neuromolecular Medicine | volume = 20 | issue = 1 | pages = 73–82 | date = March 2018 | pmid = 29332269 | doi = 10.1007/s12017-018-8476-z }}

2′-CH₃-MPTP is metabolized by monoamine oxidase A (MAO-A) and B (MAO-B) and this biotransformation is required for its dopaminergic neurotoxicity.{{cite journal | vauthors = Singer TP, Ramsay RR | title = Mechanism of the neurotoxicity of MPTP. An update | journal = FEBS Letters | volume = 274 | issue = 1–2 | pages = 1–8 | date = November 1990 | pmid = 2253761 | doi = 10.1016/0014-5793(90)81315-f }} 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.{{cite journal | vauthors = Chiueh CC, Huang SJ, Murphy DL | title = Enhanced hydroxyl radical generation by 2'-methyl analog of MPTP: suppression by clorgyline and deprenyl | journal = Synapse | volume = 11 | issue = 4 | pages = 346–348 | date = August 1992 | pmid = 1323883 | doi = 10.1002/syn.890110410 }}

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.{{cite journal | vauthors = Andrews AM, Murphy DL | title = 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 = Journal of Neurochemistry | volume = 60 | issue = 3 | pages = 1167–1170 | date = March 1993 | pmid = 8094744 | doi = 10.1111/j.1471-4159.1993.tb03271.x }} Numerous other neurotoxic MPTP analogues have also been synthesized.

2′-CH₃-MPTP was first described in the scientific literature by 1986.