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Deprenyl and
(-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent
stimulants of action potential-transmitter release coupling in the
catecholaminergic neurons.
Knoll J, Miklya I, Knoll B, Marko R,
Kelemen K.
Department of Pharmacology,
Semmelweis University of Medicine
Budapest, Hungary.
Life Sci 1996;58(10):817-827
ABSTRACT
The activity of the catecholaminergic neurons in the
rat brain is enhanced significantly 30 min after the subcutaneous injection
of very small doses of (-)deprenyl (threshold doses: 0.01 mg/kg for
noradrenergic neurons and 0.025 mg/kg for dopaminergic neurons). As a
catecholaminergic activity enhancer (CAE) substance (-)deprenyl is about ten
times more potent than its parent compound, (-)methamphetamine. While the
(+)methamphetamine is 3-5 times more potent than (-)methamphetammine in
releasing catecholamines, the (-)methamphetamine is the more potent CAE
substance.
The mechanism of the CAE effect of (-)deprenyl and (-)PPAP, a
deprenyl-derived substance devoid of MAO inhibitory potency, was studied in
rats by measuring:
a) the release of catecholamines from striatum,
substantia nigra, tuberculum olfactorium and locus coeruleus;
b) the
stimulation induced release of 3H-noradrenaline from the isolated brain
stem; and
c) the antagonistic effect against tetrabenazine-induced
depression of learning in the shuttle box.
The CAE effect was found to be
unrelated:
a) to the inhibition of MAO activity;
b) to the inhibition of
presynaptic catecholamine receptors;
c) to the inhibition of the uptake of
catecholamines; and
d) to the release of catecholamines.
It was concluded
that (-)deprenyl and (-)PPAP act primarily as potent stimulants of action
potential-transmitter release coupling in the catecholaminergic neurons of
the brain. We show that both (-)deprenyl and (-)PPAP enhance the inward Ca2+
current in sino-auricular fibers of the frog heart. (-)PPAP was much more
potent than either (+)PPAP or (-)deprenyl in this test.
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