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