L-765314 is a potent and selective antagonist of the α1b adrenergic receptor with Ki values of 5.4 nM and 2.0 nM in rat and human, respectively.
in vitro
L-765314 exhibits two displacement sites. The high-affinity site accounts for approximately 25% of binding (IC 50 ) 1.90 nM and represents binding to the R1b sites. The low- affinity site accounts for the residual 75% of binding (IC 50 ) 790 nM and represents binding to the R1a sites.
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in vivo
The results of plasma assayed by liquid chromatograph/mass spectrometer (LCMS) show that the mean C max of L-765314 (A322312) is 1.05 μM and the t 1 /2 is 0.5 h. It shows weak potency for inhibiting the pressor response to either phenylephrine or A-61603 (AD 25 >3 mg/kg for each). On the basis of the inhibition of pressor responses to the R1a subtype selective agonist A-61603, it appears to be selective versus the R1a receptor up to a dose of 0.3 mg/kg. The results of hypotensive potency in rats show that both L- 765314 and terazosin tend to decrease heart rate (about 25 bpm at 1 mg/kg iv).
