Chemistry:2′-CH3-MPTP
| File:2′-CH3-MPTP.svg | |
| Clinical data | |
|---|---|
| Other names | 2′-Methyl-MPTP |
| Drug class | Dopaminergic neurotoxin |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C13H17N |
| Molar mass | 187.286 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
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
- ↑ 1.0 1.1 1.2 "The MPTP story: MAO activates tetrahydropyridine derivatives to toxins causing parkinsonism". Drug Metabolism Reviews 22 (4): 291–332. 1990. doi:10.3109/03602539009041087. PMID 2253555.
- ↑ "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. July 1989. doi:10.1016/0006-8993(89)90065-6. PMID 2765888.
- ↑ "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. June 1989. doi:10.1007/BF03159727. PMID 2669769.
- ↑ 4.0 4.1 "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. March 1986. doi:10.1016/0014-2999(86)90115-9. PMID 3486770.
- ↑ "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. May 1990. doi:10.1016/0014-2999(90)90249-6. PMID 2117541.
- ↑ "MPTP mouse models of Parkinson's disease: an update". Journal of Parkinson's Disease 1 (1): 19–33. 2011. doi:10.3233/JPD-2011-11023. PMID 23275799.
- ↑ "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. March 2018. doi:10.1007/s12017-018-8476-z. PMID 29332269.
- ↑ 8.0 8.1 8.2 "Mechanism of the neurotoxicity of MPTP. An update". FEBS Letters 274 (1–2): 1–8. November 1990. doi:10.1016/0014-5793(90)81315-f. PMID 2253761.
- ↑ "Enhanced hydroxyl radical generation by 2'-methyl analog of MPTP: suppression by clorgyline and deprenyl". Synapse 11 (4): 346–348. August 1992. doi:10.1002/syn.890110410. PMID 1323883.
- ↑ "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. March 1993. doi:10.1111/j.1471-4159.1993.tb03271.x. PMID 8094744.
 |  |
