Annual Activities Report 2011 - INCT-Inofar - UFRJ

Annual Report 2011 | INCT-INOFAR
42
Highlights
It was elected after screening of functionalized 1,3-benzodioxolyl-N-phenylpiperazine derivatives,
synthesized from natural safrole, and unsubstituted-phenyl analogues in functional phenylephrineinduced
vasoconstriction of rabbit aorta rings bioassays. The determination of LASSBio-772 affinity for
alpha 1A (rat salivary gland) and alpha 1B (rat liver) subtypes, through displacement of [ 3 H]prazosin
specific binding, led us to obtain IC 50
values of 0.14 nM for the alpha 1A, similar to that displayed
by tamsulosin (IC 50
= 0.13 nM) [3], and 5.55 nM for the alpha 1B-AR, representing a 40-fold higher
affinity for alpha 1A over alpha 1B, in contrast to 14.8-fold for tamsulosin. LASSBio-772 also presented
high affinity (K B
= 0.025 nM) for the alpha 1D-AR subtype in functional rat aorta assays, showing to be
equipotent to tamsulosin (K B
= 0.017 nM).
Considering that LASSBio-772 showed an alpha
1-AR antagonistic action in vitro, we decided to
evaluate its effect in vivo. Analyzing the impact
of LASSBio-772 upon arterial blood pressure as
compared to a reference nonselective alpha 1-AR
antagonist (prazosin), both at the same dose (100
μg/kg), we observed that the hypotensive effect of
LASSBio-772 was significantly smaller than the
one induced by prazosin.