New compounds selective for α 1A -adrenoceptors in the prostate may offer enhanced efficacy for benign prostatic hyperplasia (BPH), with fewer side effects than current treatment. A-131701 (3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b,hexahydro-[1H]-benz[e]isoindol-2-yl)ethyl]pyrido[3′,4′:4,5]thieno [3,2-d]pyrimidine-2,4(1H,3H)-dione), from a novel class of benz[e]isolindole pyridothienopyrimidines and pyridothienopyrazines, is selective for α 1a -and α 1d -adrenoceptors in radioligand binding studies (0.22 nM at α 1a -, 0.97 nM at α 1d -) compared to α 1b -sites (2.5 nM) and in isolated tissue bioassays (pA 2 values of 8.9-9.0 for α 1A -receptors in rat vas deferens or canine prostate strips, 9.1 at α 1D -sites (rat aorta)), compared to 7.9 at α 1B -sites (rat spleen). A-131701 also potently blocked radioligand binding to α 1 -adrenoceptors in canine and human prostatic membranes, but was considerably weaker at α 2 -adrenoceptors. In isofluraneanesthetized dogs, A-131701 antagonized epinephrine-induced increases in intraurethral pressure (IUP) with a pseudo-pA 2 value of 8.17. In spontaneously hypertensive rats, A-131701 caused transient decreases in mean arterial blood pressure (MABP) and transient tachycardia. The area under the curve (AUC 0 → 60 min) for the hypotensive response was dose-related, with a log index value for A-131701 of 5.33, suggesting a