MPTP is a neurotoxin used to cause selective destruction of dopaminergic neurons in animal models of parkinsonism. MPTP is metabolized by monoamine oxidase B to produce MPDP+ and MPP+, with MP+ being the active toxic agent. MPP+ induces neurotoxicity primarily by inhibiting complex I of the mitochondrial electron transport chain, resulting in ATP depletion and increased oxidative stress. The key features of different neurotoxic models of Parkinson’s disease, including the MPTP model, have been detailed.[Cayman Chemical]
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride is a dopaminergic neurotoxin that reportedly causes a severe and irreversible Parkinsonian condition in humans and monkeys.
Purify MPTP by recrystallisation from pKEst ~ Me2CO/isoPrOH. The free base has m 40-42o(from heptane), b 99-100o/1.3mm, 128-132o/12mm, (137-142o/0.8mm), n 25 1.5347. The hydrochloride has m 251-252o(from Me2CO/isoPrOH) [Schmidle & Mansfield J Am Chem Soc 78 425 1956, Defeudis Drug Dev Res 15 1 1988, Beilstein 20 III/IV 3240, 20/7 V 121.]
[1] Lun-Yi Zang, Hara P Misra. “Inactivation of acetylcholinesterase by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride.” Molecular and Cellular Biochemistry 254 1–2 (2003): 131–6.
[2] Gregory L. Willis, Alan D. Robertson. “Recovery from experimental Parkinson’s disease in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride treated marmoset with the melatonin analogue ML-23.” Pharmacology Biochemistry and Behavior 80 1 (2005): Pages 9-26.
[3] Atsushi Fujita. “Connexin 30 deficiency attenuates A2 astrocyte responses and induces severe neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride Parkinson’s disease animal model.” Journal of Neuroinflammation (2018): 227.
