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Chemical Compound Review:

UPIDOSIN N-[3-[4-(2- methoxyphenyl)piperazin-1...

Synonyms: CHEMBL278865, AG-E-00142, SureCN6638869, ACMC-20n6iu, CHEBI:133613, ...

Leonardi, A. et al., Testa, R. et al., Rossier, O. et al., Kenny, B.A. et al., Hieble, J.P. et al.

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Disease relevance of SB 216469-S

Rec 15/2739 (SB 216469) is a novel alpha-1 adrenoceptor (alpha-1 AR) antagonist currently being developed for benign prostatic hyperplasia [1].
The urethral selectivities of Rec 15/2739 and its derivatives were confirmed by evaluation of the response to tilt in sedated, hypovolemic rabbits [2].

High impact information on SB 216469-S

The most striking difference concerns a group of N-arylpiperazines, including 8-[2-[4-(5-chloro-2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4, 5] decane-7,9-dione (REC 15/3039), REC 15/2739, and REC 15/3011, which are inverse agonists with profound negative efficacy at the wild-type alpha(1b)-AR, but not at the alpha(1a)-AR [3].
When evaluated in radioligand binding assays with expressed animal or human alpha-1 ARs, Rec 15/2739 shows marked to moderate selectivity for the alpha-1a AR subtype [1].
Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity, part I [1].
Functional studies in isolated rabbit tissues also confirmed the uroselectivity of Rec 15/2739, with substantially higher affinity (Kb = 2-3 nM) being observed in urethra and prostate, compared with ear artery and aorta (Kb = 20-100 nM) [1].
Rec 15/2739 was a more potent antagonist of phenylephrine-mediated increases in prostatic pressure ("pA2' = 8.74) compared to blood pressure ("pA2' = 7.51) [4].

Anatomical context of SB 216469-S

The aim of this study was to compare with known reference standards the functional in vitro alpha-1 antagonistic activity of Rec 15/2739 on noradrenaline-induced contractions of human prostate and mesenteric artery [5].
Functional antagonistic activity of Rec 15/2739, a novel alpha-1 antagonist selective for the lower urinary tract, on noradrenaline-induced contraction of human prostate and mesenteric artery [5].

References

Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity, part I. Leonardi, A., Hieble, J.P., Guarneri, L., Naselsky, D.P., Poggesi, E., Sironi, G., Sulpizio, A.C., Testa, R. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
Effects of alpha1-adrenoceptor antagonists on agonist and tilt-induced changes in blood pressure: relationships to uroselectivity. Hieble, J.P., Kolpak, D.C., McCafferty, G.P., Ruffolo, R.R., Testa, R., Leonardi, A. Eur. J. Pharmacol. (1999) [Pubmed]
Inverse agonism and neutral antagonism at alpha(1a)- and alpha(1b)-adrenergic receptor subtypes. Rossier, O., Abuin, L., Fanelli, F., Leonardi, A., Cotecchia, S. Mol. Pharmacol. (1999) [Pubmed]
Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies. Kenny, B.A., Miller, A.M., Williamson, I.J., O'Connell, J., Chalmers, D.H., Naylor, A.M. Br. J. Pharmacol. (1996) [Pubmed]
Functional antagonistic activity of Rec 15/2739, a novel alpha-1 antagonist selective for the lower urinary tract, on noradrenaline-induced contraction of human prostate and mesenteric artery. Testa, R., Guarneri, L., Taddei, C., Poggesi, E., Angelico, P., Sartani, A., Leonardi, A., Gofrit, O.N., Meretyk, S., Caine, M. J. Pharmacol. Exp. Ther. (1996) [Pubmed]

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