The specific topic, Isoquinolines And Beta-Carbolines As
Neurotoxins And Neuroprotectants New Perspectives In ParkinsonS
Disease Therapy, was chosen in light of accumulating
neurobiological evidence indicating that, in addition to exogenous
neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MPTP]), endogenous compounds may play an important role in the most
common neurodegenerative disorders (e.g., Parkinsons disease). Two
groups of amine related compounds, which appeared chemically like
MPTP, were detected in human brain and cerebrospinal fluid (CSF):
"ss"-carbolines (BCs) and tetrahydroisoquinolines (TIQs). These are
heterocyclic compounds formed endogenously from
phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and
5-hydroxytryptamine (BCs), respectively and exert a wide spectrum
of psychopharmacological and behavioral effects. The TIQs and BCs
may bind to their own high affinity sites on neuronal membranes
associated with or located close to the receptors of
neurotransmitters. Research on TIQs and BCs is stimulated also by
their possible role in pathological conditions, especially
parkinsonism and alcoholism. Recently, clinical interest has been
spurred by their role as neuroprotective, and even
neurorestorative, anticonvulsant and antiaddictive, substances.
In this book we are going to summarize, for the first time, the
results from behavioral, neurochemical and molecular experiments,
which demonstrate a wide spectrum of TIQs and BCs effects - from
their rather mild neurotoxic actions to the important
neuroprotective and antiaddictive properties.
Additionally, the recent results of experimental studies "in
vivo" have allowed a much better understanding and simultaneous
comparison of the neurochemical and molecular mechanisms underlying
the neuroprotective and neurotoxic actions of endogenous TIQs and
BCs and have pointed to the possibility of their therapeutic
applications in neurodegenerative diseases such as Parkinson's
disease."
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