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MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound.It is classified as a tetrahydropyridine.It is of interest as a precursor to the monoaminergic neurotoxin MPP +, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a widely used neurotoxin in Parkinson's disease research (Figure 4). In contrast to 6-OHDA, MPTP crosses the BBB which making the neurotoxin even more selective for dopaminergic neurons. Due to the ability to cross the blood-brain-barrier, MPTP is administered peripherally, subcutaneously.
A close analogue of 2′-CH 3-MPTP is 2′-NH 2-MPTP, which, in contrast to 2′-CH 3-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′-CH 3-MPTP was first described in the scientific literature by 1986. [4]
Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. [1] [2] Both hypokinetic (bradykinesia and akinesia) as well as hyperkinetic (cogwheel rigidity and tremors at rest) features are displayed by Parkinsonism. [3]
MPTP induced akinesia, rigidity, and tremor in primates, and its neurotoxicity was found to be very specific to the substantia nigra pars compacta. [58] In other animals, such as rodents, the induction of Parkinson's by MPTP is incomplete or requires much higher and frequent doses than in primates.
Stern's earliest work focused on identifying cognitive changes in nondemented patients with idiopathic Parkinson's disease, which helped identify the cognitive role of the basal ganglia when it was widely believed to have a role only in motor function. [13] He validated these observations in patients with MPTP-induced Parkinson's. [14]