Neuro-protection anyone?
.......................................................
Br J Pharmacol 2001 Jan 2;132(2):500-506
Rasagiline
Youdim MB, Gross A, Finberg JP
Technion-Rappaport Faculty of Medicine, Department of Pharmacology, Eve
Topf and
National Parkinson Foundation Centers for Neurodegenerative Diseases Research,
Haifa, Israel. Rappaport Family Research Institute, Eve Topf and National
Parkinson Foundation Centers for Neurodegenerative Diseases Research, Haifa,
Israel.
[Record supplied by publisher]
Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine
oxidase (MAO) A and B inhibitor activities in rats together with its
S(-)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to
selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were
the brain, liver and small intestine. While rasagiline and AGN1135 are highly
potent selective irreversible inhibitors of MAO in vitro and in vivo, the S(-)
enantiomer is relatively inactive in the tissues examined. The in vitro IC(50)
values for inhibition of rat brain MAO activity by rasagiline are
4.43+/-0.92 nM
(type B), and 412+/-123 nM (type A). The ED(50) values for ex vivo
inhibition of
MAO in the brain and liver by a single dose of rasagiline are 0.1+/-0.01,
0.042+/-0.0045 mg kg(-1) respectively for MAO-B, and 6.48+/-0.81,
2.38+/-0.35 mg
kg(-1) respectively for MAO-A. Selective MAO-B inhibition in the liver and brain
was maintained on chronic (21 days) oral dosage with ED(50) values of
0.014+/-0.002 and 0.013+/-0.001 mg kg(-1) respectively. The degree of
selectivity of rasagiline for inhibition of MAO-B as opposed to MAO-A was
similar to that of selegiline. Rasagiline was three to 15 times more potent than
selegiline for inhibition of MAO-B in rat brain and liver in vivo on acute and
chronic administration, but had similar potency in vitro. These data together
with lack of tyramine sympathomimetic potentiation by rasagiline, at selective
MAO-B inhibitory dosage, indicate that this inhibitor like selegiline may
be a
useful agent in the treatment of Parkinson's disease in either symptomatic or
L-DOPA adjunct therapy, but lack of amphetamine-like metabolites could
present a
therapeutic advantage for rasagiline.
PMID: 11159700
.......................................................
Ray Strand
Prairie Sky Design
-----------------( on the Edge of the Prairie Abyss )---------------
when the sky is clear
the ground is visible
49/dx PD 2 yrs/40? onset/retired
