MPTP
MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) a chemical which induces a selective dopaminergic sympathectomy that simulates ideopathic Parkinson's disease is the product of an innacurate attempted synthesis of MPPP (1-methyl-4-phenyl-4-propionoxypiperidine) from MPHP (1-methyl-4-phenyl-4-hydroxypiperide) - these are meperidine (Demerol) analoges and not amphetamine derivatives.
In 1983 a group of heroin users attempted a demerol synthesis and obtained instead a compound called MPTP. The product had a similar appearance and melting point, and they injected it expecting a demerol high. In the brain, MPTP decomposes to MPP+ which selectively bonds to and destroys dopamine receptors. These individuals thus prematurely gave themselves Parkinson's disease. MPP+ closely resembles paraquat, a defoliant used by the US government, outside US borders, against marijuana (a bit heavy handed and reckless).
In order to understand the development and behavior of central dopaminergic neurons and molecular mechanisms involved in the degeneration of such neurons in PD and MPTP-induced PD, several investigators have developed an immortalized dopaminergic cell line. The cell line is called MES 23.5 and is derived by fusion of rat embryonic mesencephalon cells with murine N18TG2 neuroblastoma cells. The cell line expresses a complex range of neural properties found in the dopaminergic neurons of the substantia nigra (Crawford et al, 1992), including tyrosine hydroxylase, dopamine synthesis, and conotoxin receptors (control of calcium channels). Only dopamine, and no other catecholamine, is synthesized by the cells. Levels of tyrosine and dopamine are elevated by 3-7 fold with the treatment of dibutyrl-cAMP. This cell line offers several advantages over other cell lines including greater homogeneity (providing more obvious and consistent observations), and susceptibility to both free radical-mediated cytotoxicity and calcium-dependent cell death.
It has been recently proposed that cerebrospinal fluid (CSF) from PD patients may possess substances which are neurotoxic for dopaminergic cells (Klawans et al, 1993; Hao et al, 1995). To define the selectivity, specificity, and property of these cytotoxic factors, investigators have employed MES 23.5 cell cultures to examine cytotoxicity of CSF from PD and non-PD patients. Preliminary studies from 5 of 7 CSF samples from PD patients, but none of 5 CSF samples from control subjects, have shown significant cytotoxic effects on MES 23.5 cells as determined by cell viability assays. The damaged cells demonstrate a pattern of apoptotic morphology including nuclear chromatin condensation and nuclear fragmentation. An approach to identify the cytotoxic factors is underway. These results raise intriguing possibilities for the etiology and pathogenesis of PD.
http://www.namiscc.org/Research/2002/Psychosis.htm
