L-765,314

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.

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).

Ki: 5.4±0.6 nM (rat α1b receptor ), 2.0±0.66 nM (human α1b receptor), 50±8 nM (rat α1d receptor), 34±6 nM (human α1d receptor), 500± 20 nM (rat α1b receptor ), 420±62 nM (human α1b receptor).